RARE DISEASE
Primary peritoneal carcinoma
Primary peritoneal carcinoma
Primary peritoneal carcinoma
Synonyms: EOPPC, Extra-ovarian primary peritoneal carcinoma, PPC, Primary peritoneal serous carcinoma, Serous surface papillary carcinoma
Synonyms: EOPPC, Extra-ovarian primary peritoneal carcinoma, PPC, Primary peritoneal serous carcinoma, Serous surface papillary carcinoma
Synonyms: EOPPC, Extra-ovarian primary peritoneal carcinoma, PPC, Primary peritoneal serous carcinoma, Serous surface papillary carcinoma
Drug discovery
7
drugs
With orphan designations
Overview
Primary peritoneal carcinoma (PPC) is a rare, aggressive malignancy arising from the peritoneal lining, clinically and histologically resembling ovarian serous carcinoma [1][3][6]. It predominantly affects postmenopausal women (median age 60–72), with BRCA1/2 mutations increasing lifetime risk by ~5% even after oophorectomy [1][3][15]. Diagnosis requires exclusion of ovarian primaries, and most present with advanced-stage disease (Stage III/IV), ascites, and elevated CA-125 [4][6][11]. Treatment mirrors ovarian cancer, combining cytoreductive surgery and platinum-taxane chemotherapy, but prognosis remains poor (median survival 12–17 months) [1][5][13].
Burden
Prognosis: Median survival 12–17 months, 5-year survival ~26% [1][4][11].
Morbidity: Advanced-stage diagnoses (70–80%) cause ascites, bowel obstruction, and cachexia, requiring palliative interventions (paracentesis, stenting) [8][15][17].
Recurrence: >75% relapse within 2 years, necessitating secondary-line therapies (gemcitabine, pegylated liposomal doxorubicin) [8][18].
Therapies
First-line: Cytoreductive surgery (optimal debulking) with hyperthermic intraperitoneal chemotherapy (HIPEC) [3][9][17], followed by platinum-paclitaxel systemic chemotherapy [8][13].
Targeted therapies: PARP inhibitors (olaparib, niraparib) for BRCA-mutated cases and bevacizumab for advanced/metastatic disease [8][13][17].
Advanced disease: Neoadjuvant chemotherapy for unresectable tumors, with interval debulking if responsive [5][8][13].
Categories: rare abdominal surgical diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
656 drug discovery papers about Primary peritoneal carcinoma, with 4 first-in-class and 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
656 drug discovery papers about Primary peritoneal carcinoma, with 4 first-in-class and 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-24 | Prospective multicenter study evaluating safety, tolerability and metabolism of niraparib as maintenance for ovarian cancer in women of African ancestry
Large-scale clinical studies investigating the safety and efficacy of novel therapeutics in ovarian cancer rarely include Black women or women of African ancestry. The sampled population in the PRIMA study was only 1.6% Black. Our objective is to evaluate the safety and tolerability of maintenance niraparib treatment in women of African ancestry. We hypothesize that the Poly (ADP-ribose) polymerase inhibitor (PARP) niraparib administered at standard doses in a population of African ancestry may demonstrate different safety and efficacy profiles to those in the PRIMA trial who were of primarily European ancestry. We will conduct a prospective, single-arm, multicenter, international study of 70 women of African ancestry designed to evaluate the safety and efficacy of niraparib maintenance therapy following completion of primary treatment for epithelial ovarian cancer. Study sites will include the United States, Bahamas, and Nigeria. Eligible patients must have histologically confirmed high-grade serous or endometrioid ovarian carcinoma, completed primary treatment for newly diagnosed stage III or IV ovarian, fallopian tube, or primary peritoneal carcinoma (surgery and chemotherapy) with partial or complete response, and self-identify as Black or African or Afro-Caribbean. The primary endpoint is the proportion of women with any grade 3 or higher adverse event. Secondary endpoints and translational endpoints will include progression free survival, pharmacokinetics, quality of life assessments, and biomarkers of PARP inhibitor resistance and metabolism. Clinical Trial Registration https://clinicaltrials.gov/study/NCT06412120 , identifier NCT06412120.
2026-09-24 | Hyperthermic intraperitoneal chemotherapy is associated with improved overall survival in advanced non-high-grade epithelial ovarian, fallopian tube, and primary peritoneal carcinoma.
Non-high-grade epithelial cancers originating in the ovary, fallopian tube, or peritoneum are rare, and the role of hyperthermic intraperitoneal chemotherapy in patients with these cancers is undefined. We evaluated whether hyperthermic intraperitoneal chemotherapy is associated with improved overall survival and, secondarily, in which histologic subgroup the association was strongest. Adults with stage III or IV non-high-grade epithelial ovarian, fallopian tube, or primary peritoneal carcinoma undergoing primary or interval cytoreductive surgery in the National Cancer Database (2004-2022) were classified by receipt of hyperthermic intraperitoneal chemotherapy. Overall survival was administratively censored at 10 years. The entire eligible cohort was analyzed with era-balanced 1:4 propensity-score matching, full-cohort inverse-probability and overlap weighting, multiple imputation, and E-values. Among 15,654 patients, 72 (0.5%) received hyperthermic intraperitoneal chemotherapy and were matched to 288 controls. In the matched cohort, 5- and 10-year overall survival were 64.5% and 48.4% with hyperthermic intraperitoneal chemotherapy versus 50.0% and 29.0% without. Hyperthermic intraperitoneal chemotherapy was associated with improved 10-year overall survival across estimators (overlap-weighted hazard ratio 0.66, 95% confidence interval 0.46 to 0.95, p = .024; inverse-probability-weighted hazard ratio 0.66, 95% confidence interval 0.47 to 0.95, p = .024; matched-set hazard ratio 0.52, 95% confidence interval 0.33 to 0.81, p = .004; multiply-imputed hazard ratio 0.66, 95% confidence interval 0.46 to 0.94, p = .023), with a directionally consistent multivariable estimate (hazard ratio 0.72, 95% confidence interval 0.49 to 1.04, p = .08). In exploratory analyses, the association was strongest in the 17 patients treated with hyperthermic intraperitoneal chemotherapy with mucinous carcinoma (multivariable hazard ratio 0.39, 95% confidence interval 0.17 to 0.88, p = .024) and was near-null in non-mucinous histologies (hazard ratio 0.93, 95% confidence interval 0.56 to 1.54); these estimates rest on small numbers. In this national cohort, hyperthermic intraperitoneal chemotherapy was associated with improved 10-year overall survival after adjustment for measured confounders, although unmeasured factors such as completeness of cytoreduction and tumor burden cannot be excluded. The association was strongest among patients with mucinous carcinoma. Pending prospective, histology-specific evaluation, these data may inform individualized discussion of hyperthermic intraperitoneal chemotherapy with selected patients at experienced centers, with counseling that high-level evidence is lacking.
2026-05-28 | Study design of OMAHA-015: A phase 2 basket study of steroidogenesis inhibitor opevesostat in participants with selected solid tumors.
TPS3183 Background: Opevesostat (MK-5684; ODM-208), an oral steroidogenesis inhibitor, selectively inhibits CYP11A1, blocking synthesis of all steroid hormones and their precursors, and may suppress steroid-driven tumor growth. The randomized, open-label, phase 2 OMAHA-015 trial (NCT06979596) is designed to evaluate the efficacy and safety of opevesostat compared with standard of care in breast, ovarian, and endometrial cancers. Methods: Cohort A will enroll participants (pts) with locally advanced unresectable or metastatic hormone receptor–positive (estrogen receptor and/or progesterone receptor ≥1% expression)/HER2-negative breast cancer (IHC 0, 1+ or 2+/ISH-) and disease progression on or after ≥1 prior endocrine-based therapy in the metastatic setting. Exclusion criteria include any line of cytotoxic chemotherapy (chemo) or PARP inhibitor in the inoperable or noncurative advanced/metastatic setting and prior treatment with both fulvestrant and exemestane in the metastatic setting. Cohort B will enroll pts with platinum-sensitive, histologically confirmed high-grade epithelial ovarian (including high-grade serous or predominantly serous, high-grade endometrioid, clear cell, or malignant mixed Müllerian tumors [carcinosarcoma]), fallopian tube, or primary peritoneal carcinomas. Pts must have received 4-8 cycles of platinum-based doublet chemo in a third-line setting for ovarian cancer with ≤9 weeks between the last dose of third-line chemo and randomization. Cohort C will enroll pts with histologically confirmed primary advanced or recurrent low-grade endometrioid carcinoma (FIGO grade 1/2, or well/moderately differentiated), with known pMMR status, and wild type p53 expression. Pts must either be treatment naive or have received 1 prior line of platinum-based therapy in the advanced/metastatic or adjuvant/neoadjuvant setting. In cohort A, ~80 pts will be randomized 1:1 to arm 1: opevesostat 5 mg PO twice daily (BID) + daily corticosteroids or arm 2: physician’s decision of fulvestrant 500 mg IM (D1 and D15 of cycle 1 and D1 of each cycle thereafter) or exemestane 25 mg PO daily. Randomization will be stratified by 1 line versus ≥2 lines of prior endocrine therapy. In cohort B, ~90 pts will be randomized 1:1 to arm 3: opevesostat 5 mg PO BID + daily corticosteroids; or arm 4: observation. In cohort C, ~80 pts will be randomized 1:1 to arm 5: opevesostat 5 mg PO BID + daily corticosteroids; or arm 6: physician’s choice of megestrol acetate 80 mg PO BID, alternating megestrol + tamoxifen 20 mg PO BID, or letrozole 2.5 mg PO daily. The primary end point is progression-free survival per RECIST v1.1 assessed by blinded independent central review (BICR). Secondary end points include overall survival, clinical benefit rate (cohort A only), objective response rate, and duration of response per RECIST v1.1 assessed by BICR, and safety. The study is currently enrolling. Clinical trial information: NCT06979596 .
2026-05-27 | Azenosertib plus paclitaxel for platinum-resistant ovarian cancer: Results from a phase 1b study.
5529 Background: Most patients (pts) with ovarian cancer develop platinum-resistant disease following surgery and platinum-based chemotherapy and have a poor prognosis. Paclitaxel (PAC) monotherapy is the most efficacious chemotherapy for platinum-resistant ovarian cancer (PROC) but clinical benefits require further improvement. Azenosertib (Azeno) is a potentially best-in-class, novel, selective and orally bioavailable small molecule inhibitor of the WEE1 tyrosine kinase. Herein we report results from a Phase 1b study of Azeno plus PAC for PROC. Methods: MUIR (NCT04516447) is an open-label Phase 1b study evaluating the safety, efficacy and preliminary clinical activity of Azeno plus chemotherapy (Part 1 dose escalation) for PROC. Eligible pts were aged ≥18 years, had ECOG PS score ≤2, histologically/cytologically confirmed high-grade serous epithelial ovarian, fallopian tube, or peritoneal carcinoma, and measurable disease per RECIST v1.1; pts had received 1‒4 prior lines of systemic therapy and had platinum-resistant disease. Pts were assigned to 1 of 4 cohorts: carboplatin, gemcitabine, pegylated liposomal doxorubicin, or PAC (80 mg/m 2 IV on Days 1, 8 and 15 of 28-day cycles). Azeno plus PAC is the focus of this analysis where Azeno was orally administered 200 mg (continuously) or 200, 250 and 300 mg (intermittently 5 days on, 2 days off [5:2]) for 28-day cycles. Primary objectives were safety and tolerability. Clinical activity was a key secondary objective assessed by objective response rate (ORR) and duration of response (DOR) per RECIST v1.1, and progression-free survival. Exploratory objectives included analysis of baseline tumor and plasma biomarkers with optional biopsies/blood plasma. Results: As of December 1, 2025, 46 pts received Azeno (continuously 200 mg, n=7 and intermittently 5:2: 200 mg, n=15; 250 mg, n=12; 300 mg, n=12) plus PAC. Median age was 66 years (range 45‒83), median number of prior lines of therapy was 2 (range, 1‒4), and all pts received prior PAC. Most common treatment related adverse events (TRAEs) were fatigue (61%), anemia (59%), nausea (52%), and neutropenia (50%); most frequent grade ≥3 TRAEs were neutropenia (30%) and anemia (20%). Serious TRAEs occurred in 20% of pts. Overall, confirmed ORR was 39.1% (95% CI, 25.1‒54.6) with a median DOR of 5.6 months (95% CI, 5.6‒9.2) (Table). Conclusions: Azeno plus PAC showed promising clinical activity and tolerability in pts with PROC. ORR and median DOR were improved when compared historically with PAC monotherapy supporting the continued evaluation of this regimen in PROC and other indications. Clinical trial information: NCT04516447 . OR and median DOR. Azeno 5:2 Azeno 5:2 Azeno 5:2 Azeno 200 mg + PAC (n=7) 200 mg + PAC (n=15) 250 mg + PAC (n=12) 300 mg + PAC (n=12) All(N=46) ORR, %(95% CI) 57.1(18.4‒90.1) 20.0(4.3‒48.1) 50.0 (21.1‒78.9) 41.7 (15.2‒72.3) 39.1 (25.1‒54.6) Median DOR, months(95% CI) 7.8(5.6‒NE) 5.6(3.7‒NE) 9.2 (3.8‒NE) 5.6 (5.2‒NE) 5.6(5.6‒9.2) NE, not evaluable.
2026-05-27 | Dose-dense weekly versus standard three-weekly paclitaxel in combination with carboplatin for resectable stage II-IV epithelial ovarian carcinoma: A retrospective cohort study.
5568 Background: Dose-dense weekly paclitaxel combined with carboplatin has demonstrated variable efficacy in first-line treatment of resectable epithelial ovarian cancer across different populations. While Japanese and selected real-world studies suggest improved outcomes, large Western trials have failed to confirm a survival advantage. Data from South Asian populations remains limited. This study compared progression-free survival (PFS), overall survival (OS), and toxicity profiles of dose-dense versus standard three-weekly paclitaxel plus carboplatin in a real-world, resource-constrained setting. Methods: This single-center retrospective cohort study included women aged ≥20 years with resectable, FIGO stage II–IV epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treated between January 2015 and December 2018. Patients received first-line carboplatin at an AUC of 5 (Area Under Curve 5) with either dose-dense weekly paclitaxel (80 mg/m² on days 1, 8, and 15) or standard three-weekly paclitaxel (175 mg/m²). Kaplan–Meier methods were used to estimate PFS and OS, and comparisons were performed using the log-rank test. Cox proportional hazards models were applied for univariate and multivariate analyses. Results: Seventy-two patients were included, 36 in each arm. The majority presented with stage III disease (63.9% in the dose-dense arm vs. 52.8% in the standard arm). High-grade serous carcinoma was the predominant histology in both groups (83% vs. 75%). The distribution of primary versus interval debulking surgery and rates of residual disease were similar between the two arms. The dose-dense regimen was associated with significantly improved PFS compared with the standard schedule (mean PFS 25 vs. 18 months; 95% CI: 23.1-28.4; log-rank p = 0.01); median PFS was 32 months in the dose-dense arm, whereas it could not be estimated in the standard arm. OS favoured the dose-dense group (mean OS of 56 vs. 50 months), although this difference was not statistically significant (p = 0.27). In the multivariate analysis of the dose-dense cohort, elevated baseline Ca-125 (HR = 6.80; 95% CI: 1.38–34.20; p = 0.01) and cytoreduction type (HR = 13.30; 95% CI: 1.90–90.20; p = 0.008) were independent predictors of PFS but not for OS. Rates of grade ≥3 treatment-related adverse events were comparable between arms, while sensory neuropathy occurred more frequently with dose-dense therapy (39% vs. 28%). Conclusions: This real-world analysis supports the use of dose-dense weekly paclitaxel combined with carboplatin for improved PFS, findings consistent with some regional studies. While OS data showed a non-significant trend favouring the dose-dense regimen with some risk of neuropathy, they highlight the need for larger prospective regional studies to better define patient populations most likely to benefit.
proteins
2026-03-22 | A retrospective analysis of risk-reducing salpingo-oophorectomy performed in women diagnosed with hereditary breast and ovarian cancer at our institution.
Hereditary breast and ovarian cancer (HBOC) confers a markedly increased lifetime risk of breast and ovarian cancers. As no effective surveillance method for early detection of ovarian cancer has been established, risk-reducing salpingo-oophorectomy (RRSO) is recommended for patients with HBOC to prevent disease onset. We evaluated the clinical characteristics of patients with HBOC and the surgical outcomes of RRSO performed at our institution. We retrospectively reviewed women diagnosed with HBOC at our institution between 2018 and 2024. For analyses of surgical outcomes, male patients, patients with prior bilateral adnexectomy, and patients diagnosed with HBOC who did not undergo RRSO were excluded. Clinical data including patient characteristics, surgical procedures, genetic testing, and pathological findings were assessed. A total of 283 women were diagnosed with HBOC, and 43 (15.1%) underwent testing based on the results of affected relatives. After excluding 39 patients with prior bilateral adnexectomy, and 105 who did not undergo RRSO, 139 patients were included in the surgical analysis. The uptake rate of RRSO among female patients with HBOC was 57%. The median age at surgery was 50 years (range, 35-75). Pathogenic BRCA1 variants were identified in 48 patients (34.5%), BRCA2 variants in 90 (64.7%), and both BRCA1 and BRCA2 variants in 1 (0.7%). A history of malignancy was observed in 121 patients (breast cancer, n = 121; pancreatic cancer, n = 1; ovarian cancer, n = 1; others, n = 3). Laparoscopic RRSO was performed in 138 cases, with one additional hysterectomy performed laparoscopically and one via laparotomy. No perioperative complications were observed. All 6 cases before April 2020 were performed outside insurance coverage; after insurance coverage was initiated in April 2020, 16 were non-covered and 117 were covered by insurance. Pathological examination revealed occult high-grade serous carcinoma in 4 patients (2.9%) and serous tubal intraepithelial carcinoma in 5 patients (3.6%). To date, no cases of primary peritoneal carcinoma following RRSO have been identified. RRSO was performed safely at our institution, with the detection rate of intraepithelial and invasive carcinoma comparable to previous reports. Although no cases of primary peritoneal carcinoma have been observed postoperatively to date, the residual risk remains, indicating the need for continued long-term surveillance.
2026-02-07 | Primary peritoneal clear cell carcinoma with metastasis mimicking ovarian carcinoma: a case report and literature review
BACKGROUND: Primary peritoneal clear cell carcinoma (PPCCC) is an exceptionally rare malignancy that closely resembles gynecologic epithelial cancers clinically and histologically. Its pathogenesis is poorly understood, with possible origins from Müllerian metaplasia or malignant transformation of endometriosis. CASE PRESENTATION: A 48-year-old woman with no history of endometriosis or hormone therapy presented with acute lower abdominal pain. Imaging revealed a pelvic mass and a lesion in the pancreatic tail. The patient underwent hysterectomy with bilateral salpingo-oophorectomy and distal pancreatectomy with splenectomy. Intraoperatively, the pelvic mass was located in the peritoneum, while the gynecologic organs appeared grossly normal. Histopathologic examination of the pelvic, pancreatic, and splenic lesions revealed identical features of clear cell carcinoma. Immunohistochemistry demonstrated positivity for PAX8, CK7, and HNF1β, with loss of MSH2 and MSH6. Next-generation sequencing revealed ARID1A loss and somatic PIK3CA mutations. No primary ovarian, endometrial, or renal tumor was detected, supporting a diagnosis of primary peritoneal clear cell carcinoma with metastases to the pancreas and spleen. CONCLUSIONS: This case highlights the diagnostic challenges of PPCCC and offers valuable insights into the clinical and pathological spectrum of this underrecognized malignancy.
2026-02-03 | Emerging trends and treatment strategies in ovarian cancer: A comprehensive review
Ovarian cancer (OC) is the eighth leading cause of cancer deaths in women globally, mainly originating from epithelial cells. It is further divided into type-I and type-II based on histology, molecular, clinical, and epidemiological characteristics. OC is commonly diagnosed in postmenopausal women, although this varies by ethnicity and genetics. Non-Hispanic white women have higher rates of OC, while African American women, despite lower incidence, are diagnosed at a younger median age. Family history and BReast CAncer gene 1&2 (BRCA1/BRCA2) mutations significantly correlate with a heightened risk of OC. Obesity, particularly from childhood, is associated with a higher risk of OC. Late menopause and smoking, are linked to a higher risk, especially for mucinous and possibly serous OC. Hormone-replacement-therapy, particularly with unopposed estrogen, also increases the risk of OC. Endometriosis raises the risk for specific subtypes like clear cell and endometrioid carcinoma. Women who have never given birth (null-parity) are at higher-risk for endometrioid and clear cell carcinoma. Surgical resection is crucial for reducing primary and local metastatic disease, involving inspection of the peritoneal cavity, cytology, lymph node removal, and biopsies. The success of surgery is limited by the visibility, extent, and tissue infiltration of the disease. The choice between neoadjuvant-chemotherapy and primary debulking surgery depends on patient health and tumor biology. Secondary cytoreductive surgery may be beneficial for platinum-sensitive recurrent OC. The use of PARP inhibitors and targeted therapies adds complexity to surgical decisions. Ongoing trials and new therapeutic strategies are expected to enhance the management and outcomes of OC.
2025-08-01 | A rare case of advanced primary peritoneal serous carcinoma: Diagnostic and therapeutic challenges of nonspecific symptoms
Abstract This case presents a 71-year-old woman with a history of hypertension and type 2 diabetes mellitus who developed vague gastrointestinal symptoms, including abdominal fullness, nausea, and significant weight loss. Through immunohistochemistry and imaging studies, she was diagnosed with advanced-stage primary peritoneal serous carcinoma (PPSC). She then underwent maximal debulking surgery, which confirmed stage IIIC PPSC with metastasis to the peritoneum, ovaries, and cervix. Her unique presentation emphasizes the critical need for heightened clinical suspicion in patients with atypical symptoms. The rarity of this diagnosis, especially at an advanced stage with nonspecific symptoms, underscores the challenge of early detection.
2021-10-28 | The Dual Effect of the BMP9–ALK1 Pathway in Blood Vessels: An Opportunity for Cancer Therapy Improvement?
The improvement of cancer therapy efficacy, the extension of patient survival and the reduction of adverse side effects are major challenges in cancer research. Targeting blood vessels has been considered a promising strategy in cancer therapy. Since the tumor vasculature is disorganized, leaky and triggers immunosuppression and tumor hypoxia, several strategies have been studied to modify tumor vasculature for cancer therapy improvement. Anti-angiogenesis was first described as a mechanism to prevent the formation of new blood vessels and prevent the oxygen supply to tumor cells, showing numerous limitations. Vascular normalization using low doses of anti-angiogenic drugs was purposed to overcome the limitations of anti-angiogenic therapies. Other strategies such as vascular promotion or the induction of high endothelial venules are being studied now to improve cancer therapy. Bone morphogenetic protein 9 (BMP9) exerts a dual effect through the activin receptor-like kinase 1 (ALK1) receptor in blood vessel maturation or activation phase of angiogenesis. Thus, it is an interesting pathway to target in combination with chemotherapies or immunotherapies. This review manuscript explores the effect of the BMP9–ALK1 pathway in tumor angiogenesis and the possible usefulness of targeting this pathway in anti-angiogenesis, vascular normalization or vascular promotion therapies.
antibodies
2026-06-09 | Single-cell transcriptomics of heterogeneous patient-derived organoids reveals novel therapeutic targets in high-grade serous ovarian cancer
Abstract High-grade serous ovarian carcinoma (HGSOC) is characterized by widespread peritoneal dissemination and poor long-term survival, largely driven by metastatic relapse following initial response to chemotherapy. Defining the molecular programs that enable tumor progression from the primary ovarian site to metastatic niches remains a key challenge. Here, we leverage patient-derived organoids (PDOs) coupled with single-cell RNA sequencing (scRNA-seq) to interrogate tumor evolution and identify regulators of metastatic competence in HGSOC. We profiled PDOs and matched formalin-fixed paraffin-embedded (FFPE) tumor samples from ovarian and omental disease sites across seven patients. Single-cell transcriptomic analysis revealed conserved and patient-specific cellular states and enabled reconstruction of inferred trajectories of tumor progression. Comparative trajectory analysis identified gene expression programs associated with metastatic transition from ovarian to omental tumors. Among these, the heparan sulfate proteoglycan AGRIN emerged as a consistently upregulated gene along the metastatic axis. Cell-cell communication analyses suggested that AGRIN -mediated signaling involves both epithelial tumor cells and stromal components, implicating the extracellular matrix in shaping metastatic behavior through mechanotransduction and integrin-associated pathways. Functional validation using genetic depletion of AGRIN in ovarian cancer cell lines demonstrated reduced migratory and invasive capacity, supporting a causal role for AGRIN in promoting metastatic phenotypes. Together, these findings identify AGRIN as a regulator of metastatic competence in HGSOC and highlight extracellular matrix–associated signaling as a key driver of disease progression. More broadly, this study demonstrates that PDO-based single-cell transcriptomic approaches can uncover actionable regulators of metastasis and provide a scalable framework for therapeutic target discovery across cancer types. Significance Patient-derived organoids analyzed by single-cell transcriptomics reveal dynamic tumor evolution and uncover AGRIN as a regulator of metastatic competence in HGSOC, demonstrating the utility of living tumor models for therapeutic target discovery.
2026-03-09 | Treatment with Mirvetuximab-Soravtansin-first clinical experience in advanced ovarian cancer in a comprehensive cancer center.
Mirvetuximab-Soravtansin (MIRV) is an antibody-drug conjugate (ADC) for the therapy of advanced platinum-resistant folate receptor α (FRα)-expressing ovarian cancer. The goal of the study was to treat patients with MIRV off-label in our Comprehensive Cancer Center regarding the outcome and adverse events. This retrospective single-center cohort study included six patients with advanced high-grade serous ovarian cancer (HGSOC) or high-grade serous primary peritoneal carcinoma (PPC) with initial FIGO stage IIC-IV between July 2023 and August 2024. Inclusion criteria were metastatic advanced HGSOC or PPC, expression of FRα ≥75% (IHC PS2+), and progression during systemic therapy with ≥3 therapies before. All patients underwent ophthalmological examination before therapy with MIRV. After 2-6 cycles of MIRV (median, 3.3), objective descriptive response with computed tomography (CT) scan of the thorax-abdomen and CA-125 response were monitored. CA-125 decreased in all evaluable patients (n, 5) from baseline. In the CT scan, two patients showed radiographically stable disease, and one of our patients represented progressive disease. Two patients revealed a partial response, and one of them had partial remission at the initial FIGO stage IV. Adverse events were monitored; one patient developed transient ocular toxicity. Treatment with MIRV has been shown to be promising in advanced ovarian cancer. In a small heterogeneous group of heavily pretreated patients, general recommendations for therapy with MIRV are limited. Close collaboration with ophthalmology and patient education is essential to mitigate ocular events.
2026-03-05 | vanallenlab/moalmanac-db: 2026 March 5th release
This release contains updates to the draft version of the database with FDA precision oncology approvals from February 2026. Specifically, indications and derived relationships were updated for Braftovi (encorafenib), Hernexeos (zongertinib), and Keytruda (pembrolizumab). Database content updates Added entries: (FDA) BRAF p.V600E and sensitivity to encorafenib in combination with cetuximab and FOLFIRI for patients with metastatic colorectal cancer. (FDA) PD-L1 (CPS >= 1) and sensitivity to pembrolizumab in combination with paclitaxel, with or without bevacizumab, for patients with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Revised entries: (FDA) BRAF p.V600E and sensitivity to encorafenib in combination with cetuximab and mFOLFOX6 for patients with metastatic colorectal cancer received regular approval. (FDA) ERBB2 activating variants and sensitivity to zongertinib in patients with non-squamous non-small cell lung cancer was revised to expand treatment eligibility by removing the prior therapy restriction. Removed entries: (EMA, HSE) FGFR2::BICC1 and FGFR2::CASP7 and sensitivity to erdafitinib in patients with bladder urothelial carcinoma. New features The Documents table was merged to align with VA-Spec. URLs associated with documents have been moved to their own table in the referenced/ folder What's Changed Adjust initial approval dates by @brendanreardon in https://github.com/vanallenlab/moalmanac-db/pull/114 Refactor documents by @brendanreardon in https://github.com/vanallenlab/moalmanac-db/pull/115 Url table by @brendanreardon in https://github.com/vanallenlab/moalmanac-db/pull/116 Ema hse adjustments by @brendanreardon in https://github.com/vanallenlab/moalmanac-db/pull/118 2026-03-02 FDA updates by @brendanreardon in https://github.com/vanallenlab/moalmanac-db/pull/120 Updated last_updated dates and PR template by @brendanreardon in https://github.com/vanallenlab/moalmanac-db/pull/121 Full Changelog: https://github.com/vanallenlab/moalmanac-db/compare/v.2026-02-05...v.2026-03-05
2026-01-07 | Performance of the VENTANA FOLR1 Assay for folate receptor alpha: Real-world evidence from 313 Chinese participants
Folate receptor-α is an ideal precision therapy target of ovarian cancer. The standardization of FRα assay and interpretative criteria is essential for ensuring diagnostic consistency and enhancing clinical efficacy in therapeutic applications. This study aims to analytically verify and evaluate the clinical performance of the VENTANA FOLR1 Assay. This real-world study of Chinese patients analyzed FRα expression using the VENTANA FOLR1 RxDx assay in 313 samples from diverse anatomical sites. Inter- and intra-observer agreement in FRα scoring was evaluated, and correlations between FRα positivity and clinicopathological parameters were examined. Three pathologists demonstrated excellent inter- and intra-observer agreement (> 97 %) in FOLR1 interpretation. 40.9 % of cases showed high FRα expression, with a significantly higher positivity rate in high-grade serous carcinoma among the Chinese cohort. Primary tumors exhibited higher FRα positivity than metastatic lesions (44.2 % vs 32.2 %, p = 0.04). Chemotherapy exposure did not significantly alter FRα positivity across ovarian, fallopian tube, and primary peritoneal cancers, remained comparable to that of the overall cohort (41.2 % vs 40.9 %). Excision/resection samples were identified as optimal for FRα assessment. Our findings demonstrate the high reliability of the VENTANA FOLR1 Assay in Chinese clinical settings. Additionally, we conducted a systematic investigation into the associations between FRα expression and clinicopathological characteristics, highlighting its capacity to reflect FRα heterogeneity, maintain stability in post-chemotherapy FRα expression across various tumor types, and achieve robust performance in excision/resection samples. These findings underscore the value of standardizing FRα testing to improve patient selection for FRα-targeted MIRV therapies in China.
2026-01-01 | Pembrolizumab in Combination with Paclitaxel for Platinum-Resistant Epithelial Ovarian, Fallopian Tube, and Primary Peritoneal Carcinoma: Clinical Evidence, Regulatory Approval and Therapeutic Implications
Background: Primary peritoneal carcinoma, fallopian tube cancer, and platinum-resistant epithelial ovarian cancer are aggressive cancers with few treatment choices and a dismal prognosis. In a variety of solid malignancies, immune checkpoint medications that target the programmed death receptor-1 (PD-1) have demonstrated encouraging activity. Objectives: To examine the clinical effectiveness, safety, and therapeutic implications of pembrolizumab in combination with paclitaxel, with or without bevacizumab, for platinum-resistant ovarian cancers that express programmed death-ligand 1 (PD-L1). This approval was recently made by the US Food and Drug Administration (FDA). Methods: Reviewed KEYNOTE-B96 (NCT05116189) clinical trial data, prescription information, and regulatory announcements. Progress-free survival (PFS) and overall survival (OS), as determined by the RECIST v1.1 criteria, were key effectiveness goals. Results: PFS was 8.3 months in the pembrolizumab arm and 7.2 months in the placebo arm for patients with PD-L1 combination positive score (CPS) ≥1 (HR 0.72; p = 0.0014). 18.2 months and 14.0 months, respectively, were the median OS (HR 0.76; p = 0.0053). The safety profile aligned with immune-related side effects linked to PD-1 inhibitors that have been documented before. Conclusion: The treatment of platinum-resistant ovarian tumors has advanced clinically with the approval of pembrolizumab in combination therapy. PD-L1 CPS-based biomarker-driven patient selection improves precision oncology methods and could lead to better survival rates in this high-risk group.
cell therapies
2026-02-01 | A 3D ovarian cancer metastasis model using a decellularised peritoneal matrix to study therapy response
BACKGROUND: High-grade serous ovarian carcinoma (HGSOC) presents a significant therapeutic challenge. Late-stage disease is frequently associated with peritoneal carcinomatosis. The peritoneal metastases exhibit a unique tumour microenvironment (TME) distinct from the primary tumours and other metastatic sites. Understanding the critical influence of the extracellular matrix (ECM) in shaping the tumour phenotype is essential for the development of effective new therapies. METHODS: This study introduces a three-dimensional (3D) model of HGSOC peritoneal metastases using a porcine decellularised peritoneal-derived ECM scaffold, referred to as peritoneal matrix (PerMa). FINDINGS: We show that the decellularisation maintains the structural integrity and composition of ECM molecules. Comparative analysis reveals structural, compositional, and mechanical similarities between porcine and human peritoneal matrices, underscoring the porcine model's translational relevance for modelling human peritoneum physiology. The PerMa supports the 3D growth of HGSOC cell lines. The model enables the assessment of sensitivity to traditional chemotherapy and novel cell-based immunotherapy through confocal imaging and quantification of cell volume. INTERPRETATION: Our model offers a valuable platform for investigating peritoneal carcinomatosis in HGSOC, with the potential to contribute significantly to developing novel therapeutic approaches. FUNDING: Financial support was provided by the University of Bergen, Helse Vest RHF (F-12183-D10616, 779, 911182, 912035, and 912146), Helse Bergen HF (240222), the Norwegian Cancer Society (6833652 and 182735), the Research Council of Norway grants (250317, 326300, 223250, 262652, and 295910), the Novo Nordisk Foundation (NNF21OC0070381), the Kolbjørn Brambani Legat for Kreftforskning, the National Institute of Health (R01CA199646) and the Swedish Cancer Society (21 1888 Pj).
2025-04-21 | Abstract 5178: Ascites conditioning reduces latency in vivo for progression of ID8 TP53 KO murine ovarian cancer model
High-grade serous ovarian carcinoma (HGSOC), an aggressive subtype of epithelial ovarian cancer (EOC) characterized by peritoneal metastasis at diagnosis and poor prognosis, is almost universally associated with p53 mutations. Mouse models of EOC and particularly HGSOC remain unsatisfactory for therapy development. Underscoring its low-grade behavior, intraperitoneal injection of the C57BL/6-derived EOC cell line ID8 from tissue culture is followed by a 9-to-10-week latency before onset of peritoneal carcinomatosis, associated with development of ascites and abdominal distention. Toward overcoming limitations of ID8 cells as a mouse model for HGSOC, Walton et al. (2018) performed CRISPR/Cas9-mediated knockout and isolated the F3 Trp53-/- cell line. While the latency period was reduced upon Trp53 deletion, 5-to-6-weeks may pass before ascites can be observed after injection of plastic-grown F3 cells. Prior studies have ascribed the delay to a dearth of cancer stem cells and/or a low propensity for colonizing the omentum. Indeed, ID8 cells isolated after 11 or 12 weeks from ascites fluid were found to be enriched for stem cells and to display immediate omental colonization and ascites onset. We confirmed that transplanting even small volumes of F3 ascites fluid into naive mice led to rapid carcinomatosis and ascites. Strikingly, passaging F3 ascites cells in tissue culture did not restore latency. These observations suggested that ascites-derived Trp53-/- ID8 cells might provide superior HGSOC models. To form an ascites-conditioned F3 cell line, CF3, plastic-grown F3 cells were injected into a C57BL/6 mouse, allowed to progress to carcinomatosis and ascites, and the ascites cells isolated and passaged four to six times. Within 14 days after being injected with CF3 cells, mice display ascites. Examining the viscera reveals visible tumors studding the abdominal mesentery and omentum. At this timepoint, mice injected with F3 display no visible signs of engraftment. CF3-injected mice reach a humane endpoint within approximately 30 days, compared to about 54 days for F3. Underlining the primary effect of ascites conditioning as reduced latency, CF3 and F3 mice display similar ascites volume, size, and distribution of metastases at their endpoints. Despite the rapid onset of carcinomatosis, CF3 cells maintain similar sensitivity to carboplatin in vivo. We suggest that ascites-conditioned cells provide a rapid and robust preclinical HGSOC model that may streamline experimental timelines and facilitate evaluation of immune and other therapies. Supported by Roswell Park-University of Chicago Ovarian Cancer SPORE P50 CA159981 and the University of Chicago Medicine Comprehensive Cancer Center. Citation Format: Taylor Barnhisel, Zari Dehdashti, Stephen Kron. Ascites conditioning reduces latency in vivo for progression of ID8 TP53 KO murine ovarian cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5178.
2024-12-29 | A 3D ovarian cancer metastasis model using a decellularized peritoneal matrix to study therapy response
Abstract High-grade serous ovarian carcinoma (HGSOC) presents a significant therapeutic challenge. Late-stage disease is frequently associated with peritoneal carcinomatosis. The peritoneal metastases exhibit a unique tumor microenvironment (TME) distinct from the primary tumors and other metastatic sites. Understanding the critical influence of the extracellular matrix (ECM) in shaping the tumor phenotype is essential for the development of effective new therapies. This study introduces a novel three-dimensional (3D) model of HGSOC peritoneal metastases using a porcine decellularized peritoneal-derived ECM scaffold, referred to as peritoneal matrix (PerMa). We show that the decellularization maintains the structural integrity and composition of ECM molecules. Comparative analysis reveals structural, compositional, and mechanical similarities between porcine and human peritoneal matrices, underscoring the porcine model’s translational relevance for modeling human peritoneum physiology. The PerMa supports the 3D growth of HGSOC cell lines. The model enables the assessment of sensitivity to traditional chemotherapy and novel cell-based immunotherapy through confocal imaging and quantification of cell volume. Our model offers a valuable platform for investigating peritoneal carcinomatosis in HGSOC, with the potential to contribute significantly to the development of novel therapeutic approaches.
2024-05-06 | Creation and Validation of Patient-Derived Cancer Model Using Peritoneal and Pleural Effusion in Patients with Advanced Ovarian Cancer: An Early Experience
Background: The application of personalized cancer treatment based on genetic information and surgical samples has begun in the field of cancer medicine. However, a biopsy may be painful for patients with advanced diseases that do not qualify for surgical resection. Patient-derived xenografts (PDXs) are cancer models in which patient samples are transplanted into immunodeficient mice. PDXs are expected to be useful for personalized medicine. The aim of this study was to establish a PDX from body fluid (PDX-BF), such as peritoneal and pleural effusion samples, to provide personalized medicine without surgery. Methods: PDXs-BF were created from patients with ovarian cancer who had positive cytology findings based on peritoneal and pleural effusion samples. PDXs were also prepared from each primary tumor. The pathological findings based on immunohistochemistry were compared between the primary tumor, PDX, and PDX-BF. Further, genomic profiles and gene expression were evaluated using DNA and RNA sequencing to compare primary tumors, PDXs, and PDX-BF. Results: Among the 15 patients, PDX-BF was established for 8 patients (5 high-grade serous carcinoma, 1 carcinosarcoma, 1 low-grade serous carcinoma, and 1 clear cell carcinoma); the success rate was 53%. Histologically, PDXs-BF have features similar to those of primary tumors and PDXs. In particular, PDXs-BF had similar gene mutations and expression patterns to primary tumors and PDXs. Conclusions: PDX-BF reproduced primary tumors in terms of pathological features and genomic profiles, including gene mutation and expression. Thus, PDX-BF may be a potential alternative to surgical resection for patients with advanced disease.
2022-09-20 | IL12 immune therapy clinical trial review: Novel strategies for avoiding CRS-associated cytokines
Interleukin 12 (IL-12) is a naturally occurring cytokine that plays a key role in inducing antitumor immune responses, including induction of antitumor immune memory. Currently, no IL-12-based therapeutic products have been approved for clinical application because of its toxicities. On the basis of this review of clinical trials using primarily wild-type IL-12 and different delivery methods, we conclude that the safe utilization of IL-12 is highly dependent on the tumor-specific localization of IL-12 post administration. In this regard, we have developed a cell membrane-anchored and tumor-targeted IL-12-T (attIL12-T) cell product for avoiding toxicity from both IL-12 and T cells-induced cytokine release syndrome in peripheral tissues. A phase I trial using this product which seeks to avoid systemic toxicity and boost antitumor efficacy is on the horizon. Of note, this product also boosts the impact of CAR-T or TCR-T cell efficacy against solid tumors, providing an alternative approach to utilize CAR-T to overcome tumor resistance.
other
2026-04-08 | Engineered Oncolytic Vaccinia Virus Strategies for High-Grade Serous Carcinoma: Intraoperative Visualisation and Autoimmune Redirection
Background: High-grade serous carcinoma (HGSC) accounts for 70–80% of ovarian cancermortality, with five-year survival for advanced disease below 25%. Immune checkpointinhibitors have failed in this indication (objective response rates 10–15%), and no oncolyticvirus is approved for ovarian cancer. Two critical unmet needs persist: incomplete surgicalcytoreduction due to the inability to detect occult peritoneal disease invisible to standardwhite-light inspection, and the absence of effective immunotherapy. Methods: Two novel oncolytic virus therapeutic concepts were developed throughsystematic review of the published clinical and preclinical literature, consultation withpractising clinicians, and structured analytical interrogation using a multi-source triangulationmethodology designed to identify consensus findings and surface areas of genuine scientificuncertainty. All conclusions were verified against primary sources. Concept 1 (Intraoperative Visualisation): A replication-competent vaccinia virus armedwith near-infrared fluorescent protein (iRFP713) and melanogenic enzymes(tyrosinase/TYRP1) to make residual HGSC deposits visible during cytoreductive surgery.Unlike passively administered fluorescent dyes, the replicating virus self-amplifiesthroughout the peritoneal tumour burden, providing four independent detection channels(NIR fluorescence, naked-eye melanin pigmentation, MRI contrast, photoacoustic imaging)from a compact ~4.2 kb payload using only 21% of the viral insertion capacity. Concept 2 (Autoimmune Redirection): A replication-competent vaccinia virus expressingthyroid autoantigens (thyroperoxidase and thyroglobulin) with immunostimulatory copayloadsto redirect pre-existing Hashimoto’s thyroiditis autoimmunity against HGSC tumourcells in the up to 10% of HGSC patients with coexisting autoimmune thyroid disease. Results: Vaccinia virus was identified as the optimal platform based on unmatchedtransgene capacity (~25 kb), established HGSC clinical data (Olvi-Vec Phase II/III), validatedintraperitoneal delivery, and existing safety infrastructure. The immunologically cold HGSCmicroenvironment, typically a barrier to immunotherapy, was identified as strategicallyadvantageous for both concepts. A dual-territory development strategy is proposed: Concept1 via Western (FDA) pathway first; Concept 2 via China-first development to exploit higherHashimoto’s prevalence in East Asian populations, with both territories pursued in parallel. Conclusions: Both concepts integrate proven, published technologies into novelcombinatorial architectures addressing distinct unmet needs in HGSC. Concept 1 offers alower-risk pathway to improving surgical outcomes; Concept 2 offers potentially curativeimmunotherapy for a defined patient subset. Both are built on a shared vaccinia backbone,enabling a single manufacturing programme.
2026-02-07 | Pembrolizumab and epigenetic modification with azacitidine reshapes the tumor microenvironment of platinum-resistant epithelial ovarian cancer: a phase 2 non-randomized clinical trial.
Epigenetic modulators may sensitize platinum-resistant ovarian cancer (PROC) to immune checkpoint inhibition by reprogramming the tumor microenvironment. We report clinical and translational findings from a phase II non-randomized study of pembrolizumab and oral azacitidine in 34 women with PROC (NCT02900560). Key eligibility criteria included age 18 years or older, performance status of 0-1, measurable disease, platinum-resistant disease and histologically confirmed epithelial ovarian cancer, fallopian tube carcinoma or primary peritoneal carcinoma. Primary endpoints included safety, tolerability, overall response rate (ORR) and disease control rate (DCR). Secondary endpoints included CA-125 response. The effect of combined epigenetic and immunotherapy was evaluated by transcriptomic analyses of 72 serially biopsied tumors. We show that the combination is moderately well tolerated and most common grade 3-4 adverse events are gastrointestinal side effects and anemia. ORR is 2.9% and DCR is 50%; with 3 of the 27 evaluable patients attaining a CA-125 response. Differential gene expression analyses reveal an upregulation of inflammatory and cytolytic genes and co-inhibitory checkpoints 6 weeks on-therapy. Upregulation of interferon signaling, antigen presentation and immune cell adhesion and migration gene sets are prominent on-therapy, together with an increase in density of CD8 + T-cells. Patients with a CA-125 and/or clinical response show an enrichment of adaptive and conserved immune response gene sets on-therapy. Our findings highlight the potential of epigenetic modulators to re-shape the tumor microenvironment of PROC toward a more inflammed phenotype and may point to approaches to augment immunotherapy response.
2025-12-12 | Safety and feasibility of talimogene laherparepvec in peritoneal surface malignancies: Results from the TEMPO trial
Peritoneal surface malignancies (PSMs) remain a therapeutic challenge, particularly in patients with unresectable disease who cannot benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. The Talimogene Laherparepvec for the Treatment of Peritoneal Surface Malignancies (TEMPO) trial (NCT03663712) is the first phase 1, multicenter, open-label study to evaluate intraperitoneal (i.p.) administration of talimogene laherparepvec (T-VEC), an FDA-approved oncolytic virus, in this setting. Nineteen patients with unresectable PSMs from appendiceal, ovarian, small bowel, and peritoneal carcinomas were enrolled; 18 received treatment across three escalating dose cohorts (4 × 106-4×108 PFU). The primary endpoint was safety and tolerability, with secondary endpoints assessing viral kinetics and shedding, and an exploratory efficacy endpoint. T-VEC demonstrated a manageable safety profile, with gastrointestinal and systemic toxicities more frequent at higher doses but no dose-limiting toxicities; one case of grade 3 neutropenia was observed. Herpes simplex virus 1 (HSV-1) DNA exhibited a dose-dependent persistence pattern, peaking later in higher dose cohorts, while plasma and urine remained consistently negative, supporting biosafety. Clinically, one complete response and ten cases of stable disease (4-19 months) were observed, while six patients experienced progression. These findings establish the safety and feasibility of i.p. T-VEC for unresectable PSMs, demonstrate localized viral replication without systemic dissemination, and suggest preliminary signals of clinical activity warranting further investigation in larger, more diverse cohorts.
2025-05-28 | Phase I study of oncolytic adenovirus BioTTT001 in patients with peritoneal carcinomatosis.
e14553 Background: The prognosis of secondary peritoneal carcinoma with malignant ascites（MA）is poor, highlighting the urgent need for new therapeutic regime. BioTTT001 is a novel oncolytic adenovirus (Ad) expressing a mutant form of interleukin-12, based on a new generation of tumor-targeted replicating oncolytic Ad backbone of human Ad5 by deleting E1A CR2 domain, E1B19K , and E3gp19K while keeping E3B genes of Ad intact. Here we report the results of the first-in-human Phase I clinical trial of BioTTT001 for the treatment of peritoneal metastasis. Methods: It's a dose-escalation, single-center clinical trial. Eligible patients (pts) had histopathologically confirmed refractory secondary peritoneal carcinomatosis from solid tumors, including gastric, colorectal and ovarian cancers. Dose escalation follows a 3+3 design at 3 dose levels. BioTTT001 is administered via intraperitoneal perfusion on days 1,3, and 5 in the first week, followed by weekly dosing for a total of 21 days per cycle. The primary endpoints include the Maximal Tolerable Dose / Recommended Phase 2 Dose (RP2D) and the incidence of adverse events. Secondary endpoints encompass preliminary clinical efficacy such as objective response rate, disease control rate (DCR), and changes in ascites volume assessed using the five-point method (5PM). The pharmacokinetics, pharmacodynamics characteristics of BioTTT001 and host immune responses to the virus were investigated as well. Results: As of Sep 30, 2024, nine pts were enrolled and received BioTTT001 intraperitoneal monotherapy (3 pts in cohort 5×10 9 vp, 3 pts in cohort 5×10 10 vp, 3 pts in cohort 1×10 10 vp). 5 pts had primary gastric cancer, 3 had ovarian cancer and 1 had rectal cancer. No DLTs were reported. Most treatment-related adverse events (TRAEs) were classified as grade 1-2; grade≥3 TRAEs including fatigue (22%), abdominal pain (11%) and lymphopenia (22%), occurred in 3/9 (33%) pts. The most common TRAEs were transient abdominal pain and fever following the virus administration. RP2D was identified as 1×10 10 vp. DCR reached 100% (5/5) among pts with measurable disease at baseline, while a reduction rate of ascites was noted at 80% (4/5) among evaluable subjects based on the 5PM. Additionally, CA125 levels decreased in 4/9 pts ( > 40% decrease observed in 2 pts). Notably, 2 pts with pelvic peritoneal metastasis exhibited significant regression of both pelvic metastases and adjacent intestinal lesions following the treatment. PCR analysis of ascites from 6 pts showed that BioTTT001 persisted in the peritoneal cavity (PC) for one week. Of note, BioTTT001 could result ineffective recruitment of CD8 + T and NK cells in PC. Conclusions: The intraperitoneal infusion of BioTTT001 for the treatment of peritoneal metastatic cancer was well tolerated with encouraging clinical benefit in pelvic peritoneal metastasis and MA controlling. This warrants further clinical investigation. Clinical trial information: ChiCTR2300069323 .
2025-05-13 | Human Papillomaviruses and Malignant Neoplasms of the Female Upper Reproductive Tract: A Comprehensive Review of the Literature
Malignancies of the female upper reproductive tract, especially endometrial and ovarian cancers, consist a significant burden for women worldwide. The possible etiopathogenetic role of chronic human papillomavirus (HPV) infection in the female upper genital tract carcinogenesis is neither clearly established not completely understood. Therefore, we performed a literature review through PubMed and SCOPUS electronic databases about the prevalence of HPV DNA in endometrial, primary fallopian tube, ovarian and primary peritoneal cancers, as well as uterine sarcomas. The present investigation covered 35 studies from different countries of various continents. Overall, HPV prevalence was approximately 15% in all the above cancers. HPV DNA was isolated from 11%, 0%, 0% and 14% of endometrial carcinomas, uterine sarcomas, primary fallopian tube cancers and ovarian malignant neoplasms, respectively. No relevant studies on primary peritoneal cancers were retrieved. The predominant HPV strain from all tumors of the upper female reproductive tract, regardless of the tumor site, was mostly HPV-16, followed by HPV-18. HPV DNA was identified exclusively from subtypes HPV-6, HPV-11, HPV-16, HPV-18, and HPV-33, which are responsible for the development of not only cervical cancer, but also of condylomata acuminata. The findings of the present review indicate that HPV vaccination might prove to be a useful strategy in the prevention HPV-related carcinomas of the upper genital tract in women.
small molecules
2026-09-24 | Prospective multicenter study evaluating safety, tolerability and metabolism of niraparib as maintenance for ovarian cancer in women of African ancestry
Large-scale clinical studies investigating the safety and efficacy of novel therapeutics in ovarian cancer rarely include Black women or women of African ancestry. The sampled population in the PRIMA study was only 1.6% Black. Our objective is to evaluate the safety and tolerability of maintenance niraparib treatment in women of African ancestry. We hypothesize that the Poly (ADP-ribose) polymerase inhibitor (PARP) niraparib administered at standard doses in a population of African ancestry may demonstrate different safety and efficacy profiles to those in the PRIMA trial who were of primarily European ancestry. We will conduct a prospective, single-arm, multicenter, international study of 70 women of African ancestry designed to evaluate the safety and efficacy of niraparib maintenance therapy following completion of primary treatment for epithelial ovarian cancer. Study sites will include the United States, Bahamas, and Nigeria. Eligible patients must have histologically confirmed high-grade serous or endometrioid ovarian carcinoma, completed primary treatment for newly diagnosed stage III or IV ovarian, fallopian tube, or primary peritoneal carcinoma (surgery and chemotherapy) with partial or complete response, and self-identify as Black or African or Afro-Caribbean. The primary endpoint is the proportion of women with any grade 3 or higher adverse event. Secondary endpoints and translational endpoints will include progression free survival, pharmacokinetics, quality of life assessments, and biomarkers of PARP inhibitor resistance and metabolism. Clinical Trial Registration https://clinicaltrials.gov/study/NCT06412120 , identifier NCT06412120.
2026-09-24 | Hyperthermic intraperitoneal chemotherapy is associated with improved overall survival in advanced non-high-grade epithelial ovarian, fallopian tube, and primary peritoneal carcinoma.
Non-high-grade epithelial cancers originating in the ovary, fallopian tube, or peritoneum are rare, and the role of hyperthermic intraperitoneal chemotherapy in patients with these cancers is undefined. We evaluated whether hyperthermic intraperitoneal chemotherapy is associated with improved overall survival and, secondarily, in which histologic subgroup the association was strongest. Adults with stage III or IV non-high-grade epithelial ovarian, fallopian tube, or primary peritoneal carcinoma undergoing primary or interval cytoreductive surgery in the National Cancer Database (2004-2022) were classified by receipt of hyperthermic intraperitoneal chemotherapy. Overall survival was administratively censored at 10 years. The entire eligible cohort was analyzed with era-balanced 1:4 propensity-score matching, full-cohort inverse-probability and overlap weighting, multiple imputation, and E-values. Among 15,654 patients, 72 (0.5%) received hyperthermic intraperitoneal chemotherapy and were matched to 288 controls. In the matched cohort, 5- and 10-year overall survival were 64.5% and 48.4% with hyperthermic intraperitoneal chemotherapy versus 50.0% and 29.0% without. Hyperthermic intraperitoneal chemotherapy was associated with improved 10-year overall survival across estimators (overlap-weighted hazard ratio 0.66, 95% confidence interval 0.46 to 0.95, p = .024; inverse-probability-weighted hazard ratio 0.66, 95% confidence interval 0.47 to 0.95, p = .024; matched-set hazard ratio 0.52, 95% confidence interval 0.33 to 0.81, p = .004; multiply-imputed hazard ratio 0.66, 95% confidence interval 0.46 to 0.94, p = .023), with a directionally consistent multivariable estimate (hazard ratio 0.72, 95% confidence interval 0.49 to 1.04, p = .08). In exploratory analyses, the association was strongest in the 17 patients treated with hyperthermic intraperitoneal chemotherapy with mucinous carcinoma (multivariable hazard ratio 0.39, 95% confidence interval 0.17 to 0.88, p = .024) and was near-null in non-mucinous histologies (hazard ratio 0.93, 95% confidence interval 0.56 to 1.54); these estimates rest on small numbers. In this national cohort, hyperthermic intraperitoneal chemotherapy was associated with improved 10-year overall survival after adjustment for measured confounders, although unmeasured factors such as completeness of cytoreduction and tumor burden cannot be excluded. The association was strongest among patients with mucinous carcinoma. Pending prospective, histology-specific evaluation, these data may inform individualized discussion of hyperthermic intraperitoneal chemotherapy with selected patients at experienced centers, with counseling that high-level evidence is lacking.
2026-05-28 | Study design of OMAHA-015: A phase 2 basket study of steroidogenesis inhibitor opevesostat in participants with selected solid tumors.
TPS3183 Background: Opevesostat (MK-5684; ODM-208), an oral steroidogenesis inhibitor, selectively inhibits CYP11A1, blocking synthesis of all steroid hormones and their precursors, and may suppress steroid-driven tumor growth. The randomized, open-label, phase 2 OMAHA-015 trial (NCT06979596) is designed to evaluate the efficacy and safety of opevesostat compared with standard of care in breast, ovarian, and endometrial cancers. Methods: Cohort A will enroll participants (pts) with locally advanced unresectable or metastatic hormone receptor–positive (estrogen receptor and/or progesterone receptor ≥1% expression)/HER2-negative breast cancer (IHC 0, 1+ or 2+/ISH-) and disease progression on or after ≥1 prior endocrine-based therapy in the metastatic setting. Exclusion criteria include any line of cytotoxic chemotherapy (chemo) or PARP inhibitor in the inoperable or noncurative advanced/metastatic setting and prior treatment with both fulvestrant and exemestane in the metastatic setting. Cohort B will enroll pts with platinum-sensitive, histologically confirmed high-grade epithelial ovarian (including high-grade serous or predominantly serous, high-grade endometrioid, clear cell, or malignant mixed Müllerian tumors [carcinosarcoma]), fallopian tube, or primary peritoneal carcinomas. Pts must have received 4-8 cycles of platinum-based doublet chemo in a third-line setting for ovarian cancer with ≤9 weeks between the last dose of third-line chemo and randomization. Cohort C will enroll pts with histologically confirmed primary advanced or recurrent low-grade endometrioid carcinoma (FIGO grade 1/2, or well/moderately differentiated), with known pMMR status, and wild type p53 expression. Pts must either be treatment naive or have received 1 prior line of platinum-based therapy in the advanced/metastatic or adjuvant/neoadjuvant setting. In cohort A, ~80 pts will be randomized 1:1 to arm 1: opevesostat 5 mg PO twice daily (BID) + daily corticosteroids or arm 2: physician’s decision of fulvestrant 500 mg IM (D1 and D15 of cycle 1 and D1 of each cycle thereafter) or exemestane 25 mg PO daily. Randomization will be stratified by 1 line versus ≥2 lines of prior endocrine therapy. In cohort B, ~90 pts will be randomized 1:1 to arm 3: opevesostat 5 mg PO BID + daily corticosteroids; or arm 4: observation. In cohort C, ~80 pts will be randomized 1:1 to arm 5: opevesostat 5 mg PO BID + daily corticosteroids; or arm 6: physician’s choice of megestrol acetate 80 mg PO BID, alternating megestrol + tamoxifen 20 mg PO BID, or letrozole 2.5 mg PO daily. The primary end point is progression-free survival per RECIST v1.1 assessed by blinded independent central review (BICR). Secondary end points include overall survival, clinical benefit rate (cohort A only), objective response rate, and duration of response per RECIST v1.1 assessed by BICR, and safety. The study is currently enrolling. Clinical trial information: NCT06979596 .
2026-05-27 | Azenosertib plus paclitaxel for platinum-resistant ovarian cancer: Results from a phase 1b study.
5529 Background: Most patients (pts) with ovarian cancer develop platinum-resistant disease following surgery and platinum-based chemotherapy and have a poor prognosis. Paclitaxel (PAC) monotherapy is the most efficacious chemotherapy for platinum-resistant ovarian cancer (PROC) but clinical benefits require further improvement. Azenosertib (Azeno) is a potentially best-in-class, novel, selective and orally bioavailable small molecule inhibitor of the WEE1 tyrosine kinase. Herein we report results from a Phase 1b study of Azeno plus PAC for PROC. Methods: MUIR (NCT04516447) is an open-label Phase 1b study evaluating the safety, efficacy and preliminary clinical activity of Azeno plus chemotherapy (Part 1 dose escalation) for PROC. Eligible pts were aged ≥18 years, had ECOG PS score ≤2, histologically/cytologically confirmed high-grade serous epithelial ovarian, fallopian tube, or peritoneal carcinoma, and measurable disease per RECIST v1.1; pts had received 1‒4 prior lines of systemic therapy and had platinum-resistant disease. Pts were assigned to 1 of 4 cohorts: carboplatin, gemcitabine, pegylated liposomal doxorubicin, or PAC (80 mg/m 2 IV on Days 1, 8 and 15 of 28-day cycles). Azeno plus PAC is the focus of this analysis where Azeno was orally administered 200 mg (continuously) or 200, 250 and 300 mg (intermittently 5 days on, 2 days off [5:2]) for 28-day cycles. Primary objectives were safety and tolerability. Clinical activity was a key secondary objective assessed by objective response rate (ORR) and duration of response (DOR) per RECIST v1.1, and progression-free survival. Exploratory objectives included analysis of baseline tumor and plasma biomarkers with optional biopsies/blood plasma. Results: As of December 1, 2025, 46 pts received Azeno (continuously 200 mg, n=7 and intermittently 5:2: 200 mg, n=15; 250 mg, n=12; 300 mg, n=12) plus PAC. Median age was 66 years (range 45‒83), median number of prior lines of therapy was 2 (range, 1‒4), and all pts received prior PAC. Most common treatment related adverse events (TRAEs) were fatigue (61%), anemia (59%), nausea (52%), and neutropenia (50%); most frequent grade ≥3 TRAEs were neutropenia (30%) and anemia (20%). Serious TRAEs occurred in 20% of pts. Overall, confirmed ORR was 39.1% (95% CI, 25.1‒54.6) with a median DOR of 5.6 months (95% CI, 5.6‒9.2) (Table). Conclusions: Azeno plus PAC showed promising clinical activity and tolerability in pts with PROC. ORR and median DOR were improved when compared historically with PAC monotherapy supporting the continued evaluation of this regimen in PROC and other indications. Clinical trial information: NCT04516447 . OR and median DOR. Azeno 5:2 Azeno 5:2 Azeno 5:2 Azeno 200 mg + PAC (n=7) 200 mg + PAC (n=15) 250 mg + PAC (n=12) 300 mg + PAC (n=12) All(N=46) ORR, %(95% CI) 57.1(18.4‒90.1) 20.0(4.3‒48.1) 50.0 (21.1‒78.9) 41.7 (15.2‒72.3) 39.1 (25.1‒54.6) Median DOR, months(95% CI) 7.8(5.6‒NE) 5.6(3.7‒NE) 9.2 (3.8‒NE) 5.6 (5.2‒NE) 5.6(5.6‒9.2) NE, not evaluable.
2026-05-27 | Dose-dense weekly versus standard three-weekly paclitaxel in combination with carboplatin for resectable stage II-IV epithelial ovarian carcinoma: A retrospective cohort study.
5568 Background: Dose-dense weekly paclitaxel combined with carboplatin has demonstrated variable efficacy in first-line treatment of resectable epithelial ovarian cancer across different populations. While Japanese and selected real-world studies suggest improved outcomes, large Western trials have failed to confirm a survival advantage. Data from South Asian populations remains limited. This study compared progression-free survival (PFS), overall survival (OS), and toxicity profiles of dose-dense versus standard three-weekly paclitaxel plus carboplatin in a real-world, resource-constrained setting. Methods: This single-center retrospective cohort study included women aged ≥20 years with resectable, FIGO stage II–IV epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treated between January 2015 and December 2018. Patients received first-line carboplatin at an AUC of 5 (Area Under Curve 5) with either dose-dense weekly paclitaxel (80 mg/m² on days 1, 8, and 15) or standard three-weekly paclitaxel (175 mg/m²). Kaplan–Meier methods were used to estimate PFS and OS, and comparisons were performed using the log-rank test. Cox proportional hazards models were applied for univariate and multivariate analyses. Results: Seventy-two patients were included, 36 in each arm. The majority presented with stage III disease (63.9% in the dose-dense arm vs. 52.8% in the standard arm). High-grade serous carcinoma was the predominant histology in both groups (83% vs. 75%). The distribution of primary versus interval debulking surgery and rates of residual disease were similar between the two arms. The dose-dense regimen was associated with significantly improved PFS compared with the standard schedule (mean PFS 25 vs. 18 months; 95% CI: 23.1-28.4; log-rank p = 0.01); median PFS was 32 months in the dose-dense arm, whereas it could not be estimated in the standard arm. OS favoured the dose-dense group (mean OS of 56 vs. 50 months), although this difference was not statistically significant (p = 0.27). In the multivariate analysis of the dose-dense cohort, elevated baseline Ca-125 (HR = 6.80; 95% CI: 1.38–34.20; p = 0.01) and cytoreduction type (HR = 13.30; 95% CI: 1.90–90.20; p = 0.008) were independent predictors of PFS but not for OS. Rates of grade ≥3 treatment-related adverse events were comparable between arms, while sensory neuropathy occurred more frequently with dose-dense therapy (39% vs. 28%). Conclusions: This real-world analysis supports the use of dose-dense weekly paclitaxel combined with carboplatin for improved PFS, findings consistent with some regional studies. While OS data showed a non-significant trend favouring the dose-dense regimen with some risk of neuropathy, they highlight the need for larger prospective regional studies to better define patient populations most likely to benefit.
proteins
2026-03-22 | A retrospective analysis of risk-reducing salpingo-oophorectomy performed in women diagnosed with hereditary breast and ovarian cancer at our institution.
Hereditary breast and ovarian cancer (HBOC) confers a markedly increased lifetime risk of breast and ovarian cancers. As no effective surveillance method for early detection of ovarian cancer has been established, risk-reducing salpingo-oophorectomy (RRSO) is recommended for patients with HBOC to prevent disease onset. We evaluated the clinical characteristics of patients with HBOC and the surgical outcomes of RRSO performed at our institution. We retrospectively reviewed women diagnosed with HBOC at our institution between 2018 and 2024. For analyses of surgical outcomes, male patients, patients with prior bilateral adnexectomy, and patients diagnosed with HBOC who did not undergo RRSO were excluded. Clinical data including patient characteristics, surgical procedures, genetic testing, and pathological findings were assessed. A total of 283 women were diagnosed with HBOC, and 43 (15.1%) underwent testing based on the results of affected relatives. After excluding 39 patients with prior bilateral adnexectomy, and 105 who did not undergo RRSO, 139 patients were included in the surgical analysis. The uptake rate of RRSO among female patients with HBOC was 57%. The median age at surgery was 50 years (range, 35-75). Pathogenic BRCA1 variants were identified in 48 patients (34.5%), BRCA2 variants in 90 (64.7%), and both BRCA1 and BRCA2 variants in 1 (0.7%). A history of malignancy was observed in 121 patients (breast cancer, n = 121; pancreatic cancer, n = 1; ovarian cancer, n = 1; others, n = 3). Laparoscopic RRSO was performed in 138 cases, with one additional hysterectomy performed laparoscopically and one via laparotomy. No perioperative complications were observed. All 6 cases before April 2020 were performed outside insurance coverage; after insurance coverage was initiated in April 2020, 16 were non-covered and 117 were covered by insurance. Pathological examination revealed occult high-grade serous carcinoma in 4 patients (2.9%) and serous tubal intraepithelial carcinoma in 5 patients (3.6%). To date, no cases of primary peritoneal carcinoma following RRSO have been identified. RRSO was performed safely at our institution, with the detection rate of intraepithelial and invasive carcinoma comparable to previous reports. Although no cases of primary peritoneal carcinoma have been observed postoperatively to date, the residual risk remains, indicating the need for continued long-term surveillance.
2026-02-07 | Primary peritoneal clear cell carcinoma with metastasis mimicking ovarian carcinoma: a case report and literature review
BACKGROUND: Primary peritoneal clear cell carcinoma (PPCCC) is an exceptionally rare malignancy that closely resembles gynecologic epithelial cancers clinically and histologically. Its pathogenesis is poorly understood, with possible origins from Müllerian metaplasia or malignant transformation of endometriosis. CASE PRESENTATION: A 48-year-old woman with no history of endometriosis or hormone therapy presented with acute lower abdominal pain. Imaging revealed a pelvic mass and a lesion in the pancreatic tail. The patient underwent hysterectomy with bilateral salpingo-oophorectomy and distal pancreatectomy with splenectomy. Intraoperatively, the pelvic mass was located in the peritoneum, while the gynecologic organs appeared grossly normal. Histopathologic examination of the pelvic, pancreatic, and splenic lesions revealed identical features of clear cell carcinoma. Immunohistochemistry demonstrated positivity for PAX8, CK7, and HNF1β, with loss of MSH2 and MSH6. Next-generation sequencing revealed ARID1A loss and somatic PIK3CA mutations. No primary ovarian, endometrial, or renal tumor was detected, supporting a diagnosis of primary peritoneal clear cell carcinoma with metastases to the pancreas and spleen. CONCLUSIONS: This case highlights the diagnostic challenges of PPCCC and offers valuable insights into the clinical and pathological spectrum of this underrecognized malignancy.
2026-02-03 | Emerging trends and treatment strategies in ovarian cancer: A comprehensive review
Ovarian cancer (OC) is the eighth leading cause of cancer deaths in women globally, mainly originating from epithelial cells. It is further divided into type-I and type-II based on histology, molecular, clinical, and epidemiological characteristics. OC is commonly diagnosed in postmenopausal women, although this varies by ethnicity and genetics. Non-Hispanic white women have higher rates of OC, while African American women, despite lower incidence, are diagnosed at a younger median age. Family history and BReast CAncer gene 1&2 (BRCA1/BRCA2) mutations significantly correlate with a heightened risk of OC. Obesity, particularly from childhood, is associated with a higher risk of OC. Late menopause and smoking, are linked to a higher risk, especially for mucinous and possibly serous OC. Hormone-replacement-therapy, particularly with unopposed estrogen, also increases the risk of OC. Endometriosis raises the risk for specific subtypes like clear cell and endometrioid carcinoma. Women who have never given birth (null-parity) are at higher-risk for endometrioid and clear cell carcinoma. Surgical resection is crucial for reducing primary and local metastatic disease, involving inspection of the peritoneal cavity, cytology, lymph node removal, and biopsies. The success of surgery is limited by the visibility, extent, and tissue infiltration of the disease. The choice between neoadjuvant-chemotherapy and primary debulking surgery depends on patient health and tumor biology. Secondary cytoreductive surgery may be beneficial for platinum-sensitive recurrent OC. The use of PARP inhibitors and targeted therapies adds complexity to surgical decisions. Ongoing trials and new therapeutic strategies are expected to enhance the management and outcomes of OC.
2025-08-01 | A rare case of advanced primary peritoneal serous carcinoma: Diagnostic and therapeutic challenges of nonspecific symptoms
Abstract This case presents a 71-year-old woman with a history of hypertension and type 2 diabetes mellitus who developed vague gastrointestinal symptoms, including abdominal fullness, nausea, and significant weight loss. Through immunohistochemistry and imaging studies, she was diagnosed with advanced-stage primary peritoneal serous carcinoma (PPSC). She then underwent maximal debulking surgery, which confirmed stage IIIC PPSC with metastasis to the peritoneum, ovaries, and cervix. Her unique presentation emphasizes the critical need for heightened clinical suspicion in patients with atypical symptoms. The rarity of this diagnosis, especially at an advanced stage with nonspecific symptoms, underscores the challenge of early detection.
2021-10-28 | The Dual Effect of the BMP9–ALK1 Pathway in Blood Vessels: An Opportunity for Cancer Therapy Improvement?
The improvement of cancer therapy efficacy, the extension of patient survival and the reduction of adverse side effects are major challenges in cancer research. Targeting blood vessels has been considered a promising strategy in cancer therapy. Since the tumor vasculature is disorganized, leaky and triggers immunosuppression and tumor hypoxia, several strategies have been studied to modify tumor vasculature for cancer therapy improvement. Anti-angiogenesis was first described as a mechanism to prevent the formation of new blood vessels and prevent the oxygen supply to tumor cells, showing numerous limitations. Vascular normalization using low doses of anti-angiogenic drugs was purposed to overcome the limitations of anti-angiogenic therapies. Other strategies such as vascular promotion or the induction of high endothelial venules are being studied now to improve cancer therapy. Bone morphogenetic protein 9 (BMP9) exerts a dual effect through the activin receptor-like kinase 1 (ALK1) receptor in blood vessel maturation or activation phase of angiogenesis. Thus, it is an interesting pathway to target in combination with chemotherapies or immunotherapies. This review manuscript explores the effect of the BMP9–ALK1 pathway in tumor angiogenesis and the possible usefulness of targeting this pathway in anti-angiogenesis, vascular normalization or vascular promotion therapies.
antibodies
2026-06-09 | Single-cell transcriptomics of heterogeneous patient-derived organoids reveals novel therapeutic targets in high-grade serous ovarian cancer
Abstract High-grade serous ovarian carcinoma (HGSOC) is characterized by widespread peritoneal dissemination and poor long-term survival, largely driven by metastatic relapse following initial response to chemotherapy. Defining the molecular programs that enable tumor progression from the primary ovarian site to metastatic niches remains a key challenge. Here, we leverage patient-derived organoids (PDOs) coupled with single-cell RNA sequencing (scRNA-seq) to interrogate tumor evolution and identify regulators of metastatic competence in HGSOC. We profiled PDOs and matched formalin-fixed paraffin-embedded (FFPE) tumor samples from ovarian and omental disease sites across seven patients. Single-cell transcriptomic analysis revealed conserved and patient-specific cellular states and enabled reconstruction of inferred trajectories of tumor progression. Comparative trajectory analysis identified gene expression programs associated with metastatic transition from ovarian to omental tumors. Among these, the heparan sulfate proteoglycan AGRIN emerged as a consistently upregulated gene along the metastatic axis. Cell-cell communication analyses suggested that AGRIN -mediated signaling involves both epithelial tumor cells and stromal components, implicating the extracellular matrix in shaping metastatic behavior through mechanotransduction and integrin-associated pathways. Functional validation using genetic depletion of AGRIN in ovarian cancer cell lines demonstrated reduced migratory and invasive capacity, supporting a causal role for AGRIN in promoting metastatic phenotypes. Together, these findings identify AGRIN as a regulator of metastatic competence in HGSOC and highlight extracellular matrix–associated signaling as a key driver of disease progression. More broadly, this study demonstrates that PDO-based single-cell transcriptomic approaches can uncover actionable regulators of metastasis and provide a scalable framework for therapeutic target discovery across cancer types. Significance Patient-derived organoids analyzed by single-cell transcriptomics reveal dynamic tumor evolution and uncover AGRIN as a regulator of metastatic competence in HGSOC, demonstrating the utility of living tumor models for therapeutic target discovery.
2026-03-09 | Treatment with Mirvetuximab-Soravtansin-first clinical experience in advanced ovarian cancer in a comprehensive cancer center.
Mirvetuximab-Soravtansin (MIRV) is an antibody-drug conjugate (ADC) for the therapy of advanced platinum-resistant folate receptor α (FRα)-expressing ovarian cancer. The goal of the study was to treat patients with MIRV off-label in our Comprehensive Cancer Center regarding the outcome and adverse events. This retrospective single-center cohort study included six patients with advanced high-grade serous ovarian cancer (HGSOC) or high-grade serous primary peritoneal carcinoma (PPC) with initial FIGO stage IIC-IV between July 2023 and August 2024. Inclusion criteria were metastatic advanced HGSOC or PPC, expression of FRα ≥75% (IHC PS2+), and progression during systemic therapy with ≥3 therapies before. All patients underwent ophthalmological examination before therapy with MIRV. After 2-6 cycles of MIRV (median, 3.3), objective descriptive response with computed tomography (CT) scan of the thorax-abdomen and CA-125 response were monitored. CA-125 decreased in all evaluable patients (n, 5) from baseline. In the CT scan, two patients showed radiographically stable disease, and one of our patients represented progressive disease. Two patients revealed a partial response, and one of them had partial remission at the initial FIGO stage IV. Adverse events were monitored; one patient developed transient ocular toxicity. Treatment with MIRV has been shown to be promising in advanced ovarian cancer. In a small heterogeneous group of heavily pretreated patients, general recommendations for therapy with MIRV are limited. Close collaboration with ophthalmology and patient education is essential to mitigate ocular events.
2026-03-05 | vanallenlab/moalmanac-db: 2026 March 5th release
This release contains updates to the draft version of the database with FDA precision oncology approvals from February 2026. Specifically, indications and derived relationships were updated for Braftovi (encorafenib), Hernexeos (zongertinib), and Keytruda (pembrolizumab). Database content updates Added entries: (FDA) BRAF p.V600E and sensitivity to encorafenib in combination with cetuximab and FOLFIRI for patients with metastatic colorectal cancer. (FDA) PD-L1 (CPS >= 1) and sensitivity to pembrolizumab in combination with paclitaxel, with or without bevacizumab, for patients with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Revised entries: (FDA) BRAF p.V600E and sensitivity to encorafenib in combination with cetuximab and mFOLFOX6 for patients with metastatic colorectal cancer received regular approval. (FDA) ERBB2 activating variants and sensitivity to zongertinib in patients with non-squamous non-small cell lung cancer was revised to expand treatment eligibility by removing the prior therapy restriction. Removed entries: (EMA, HSE) FGFR2::BICC1 and FGFR2::CASP7 and sensitivity to erdafitinib in patients with bladder urothelial carcinoma. New features The Documents table was merged to align with VA-Spec. URLs associated with documents have been moved to their own table in the referenced/ folder What's Changed Adjust initial approval dates by @brendanreardon in https://github.com/vanallenlab/moalmanac-db/pull/114 Refactor documents by @brendanreardon in https://github.com/vanallenlab/moalmanac-db/pull/115 Url table by @brendanreardon in https://github.com/vanallenlab/moalmanac-db/pull/116 Ema hse adjustments by @brendanreardon in https://github.com/vanallenlab/moalmanac-db/pull/118 2026-03-02 FDA updates by @brendanreardon in https://github.com/vanallenlab/moalmanac-db/pull/120 Updated last_updated dates and PR template by @brendanreardon in https://github.com/vanallenlab/moalmanac-db/pull/121 Full Changelog: https://github.com/vanallenlab/moalmanac-db/compare/v.2026-02-05...v.2026-03-05
2026-01-07 | Performance of the VENTANA FOLR1 Assay for folate receptor alpha: Real-world evidence from 313 Chinese participants
Folate receptor-α is an ideal precision therapy target of ovarian cancer. The standardization of FRα assay and interpretative criteria is essential for ensuring diagnostic consistency and enhancing clinical efficacy in therapeutic applications. This study aims to analytically verify and evaluate the clinical performance of the VENTANA FOLR1 Assay. This real-world study of Chinese patients analyzed FRα expression using the VENTANA FOLR1 RxDx assay in 313 samples from diverse anatomical sites. Inter- and intra-observer agreement in FRα scoring was evaluated, and correlations between FRα positivity and clinicopathological parameters were examined. Three pathologists demonstrated excellent inter- and intra-observer agreement (> 97 %) in FOLR1 interpretation. 40.9 % of cases showed high FRα expression, with a significantly higher positivity rate in high-grade serous carcinoma among the Chinese cohort. Primary tumors exhibited higher FRα positivity than metastatic lesions (44.2 % vs 32.2 %, p = 0.04). Chemotherapy exposure did not significantly alter FRα positivity across ovarian, fallopian tube, and primary peritoneal cancers, remained comparable to that of the overall cohort (41.2 % vs 40.9 %). Excision/resection samples were identified as optimal for FRα assessment. Our findings demonstrate the high reliability of the VENTANA FOLR1 Assay in Chinese clinical settings. Additionally, we conducted a systematic investigation into the associations between FRα expression and clinicopathological characteristics, highlighting its capacity to reflect FRα heterogeneity, maintain stability in post-chemotherapy FRα expression across various tumor types, and achieve robust performance in excision/resection samples. These findings underscore the value of standardizing FRα testing to improve patient selection for FRα-targeted MIRV therapies in China.
2026-01-01 | Pembrolizumab in Combination with Paclitaxel for Platinum-Resistant Epithelial Ovarian, Fallopian Tube, and Primary Peritoneal Carcinoma: Clinical Evidence, Regulatory Approval and Therapeutic Implications
Background: Primary peritoneal carcinoma, fallopian tube cancer, and platinum-resistant epithelial ovarian cancer are aggressive cancers with few treatment choices and a dismal prognosis. In a variety of solid malignancies, immune checkpoint medications that target the programmed death receptor-1 (PD-1) have demonstrated encouraging activity. Objectives: To examine the clinical effectiveness, safety, and therapeutic implications of pembrolizumab in combination with paclitaxel, with or without bevacizumab, for platinum-resistant ovarian cancers that express programmed death-ligand 1 (PD-L1). This approval was recently made by the US Food and Drug Administration (FDA). Methods: Reviewed KEYNOTE-B96 (NCT05116189) clinical trial data, prescription information, and regulatory announcements. Progress-free survival (PFS) and overall survival (OS), as determined by the RECIST v1.1 criteria, were key effectiveness goals. Results: PFS was 8.3 months in the pembrolizumab arm and 7.2 months in the placebo arm for patients with PD-L1 combination positive score (CPS) ≥1 (HR 0.72; p = 0.0014). 18.2 months and 14.0 months, respectively, were the median OS (HR 0.76; p = 0.0053). The safety profile aligned with immune-related side effects linked to PD-1 inhibitors that have been documented before. Conclusion: The treatment of platinum-resistant ovarian tumors has advanced clinically with the approval of pembrolizumab in combination therapy. PD-L1 CPS-based biomarker-driven patient selection improves precision oncology methods and could lead to better survival rates in this high-risk group.
cell therapies
2026-02-01 | A 3D ovarian cancer metastasis model using a decellularised peritoneal matrix to study therapy response
BACKGROUND: High-grade serous ovarian carcinoma (HGSOC) presents a significant therapeutic challenge. Late-stage disease is frequently associated with peritoneal carcinomatosis. The peritoneal metastases exhibit a unique tumour microenvironment (TME) distinct from the primary tumours and other metastatic sites. Understanding the critical influence of the extracellular matrix (ECM) in shaping the tumour phenotype is essential for the development of effective new therapies. METHODS: This study introduces a three-dimensional (3D) model of HGSOC peritoneal metastases using a porcine decellularised peritoneal-derived ECM scaffold, referred to as peritoneal matrix (PerMa). FINDINGS: We show that the decellularisation maintains the structural integrity and composition of ECM molecules. Comparative analysis reveals structural, compositional, and mechanical similarities between porcine and human peritoneal matrices, underscoring the porcine model's translational relevance for modelling human peritoneum physiology. The PerMa supports the 3D growth of HGSOC cell lines. The model enables the assessment of sensitivity to traditional chemotherapy and novel cell-based immunotherapy through confocal imaging and quantification of cell volume. INTERPRETATION: Our model offers a valuable platform for investigating peritoneal carcinomatosis in HGSOC, with the potential to contribute significantly to developing novel therapeutic approaches. FUNDING: Financial support was provided by the University of Bergen, Helse Vest RHF (F-12183-D10616, 779, 911182, 912035, and 912146), Helse Bergen HF (240222), the Norwegian Cancer Society (6833652 and 182735), the Research Council of Norway grants (250317, 326300, 223250, 262652, and 295910), the Novo Nordisk Foundation (NNF21OC0070381), the Kolbjørn Brambani Legat for Kreftforskning, the National Institute of Health (R01CA199646) and the Swedish Cancer Society (21 1888 Pj).
2025-04-21 | Abstract 5178: Ascites conditioning reduces latency in vivo for progression of ID8 TP53 KO murine ovarian cancer model
High-grade serous ovarian carcinoma (HGSOC), an aggressive subtype of epithelial ovarian cancer (EOC) characterized by peritoneal metastasis at diagnosis and poor prognosis, is almost universally associated with p53 mutations. Mouse models of EOC and particularly HGSOC remain unsatisfactory for therapy development. Underscoring its low-grade behavior, intraperitoneal injection of the C57BL/6-derived EOC cell line ID8 from tissue culture is followed by a 9-to-10-week latency before onset of peritoneal carcinomatosis, associated with development of ascites and abdominal distention. Toward overcoming limitations of ID8 cells as a mouse model for HGSOC, Walton et al. (2018) performed CRISPR/Cas9-mediated knockout and isolated the F3 Trp53-/- cell line. While the latency period was reduced upon Trp53 deletion, 5-to-6-weeks may pass before ascites can be observed after injection of plastic-grown F3 cells. Prior studies have ascribed the delay to a dearth of cancer stem cells and/or a low propensity for colonizing the omentum. Indeed, ID8 cells isolated after 11 or 12 weeks from ascites fluid were found to be enriched for stem cells and to display immediate omental colonization and ascites onset. We confirmed that transplanting even small volumes of F3 ascites fluid into naive mice led to rapid carcinomatosis and ascites. Strikingly, passaging F3 ascites cells in tissue culture did not restore latency. These observations suggested that ascites-derived Trp53-/- ID8 cells might provide superior HGSOC models. To form an ascites-conditioned F3 cell line, CF3, plastic-grown F3 cells were injected into a C57BL/6 mouse, allowed to progress to carcinomatosis and ascites, and the ascites cells isolated and passaged four to six times. Within 14 days after being injected with CF3 cells, mice display ascites. Examining the viscera reveals visible tumors studding the abdominal mesentery and omentum. At this timepoint, mice injected with F3 display no visible signs of engraftment. CF3-injected mice reach a humane endpoint within approximately 30 days, compared to about 54 days for F3. Underlining the primary effect of ascites conditioning as reduced latency, CF3 and F3 mice display similar ascites volume, size, and distribution of metastases at their endpoints. Despite the rapid onset of carcinomatosis, CF3 cells maintain similar sensitivity to carboplatin in vivo. We suggest that ascites-conditioned cells provide a rapid and robust preclinical HGSOC model that may streamline experimental timelines and facilitate evaluation of immune and other therapies. Supported by Roswell Park-University of Chicago Ovarian Cancer SPORE P50 CA159981 and the University of Chicago Medicine Comprehensive Cancer Center. Citation Format: Taylor Barnhisel, Zari Dehdashti, Stephen Kron. Ascites conditioning reduces latency in vivo for progression of ID8 TP53 KO murine ovarian cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5178.
2024-12-29 | A 3D ovarian cancer metastasis model using a decellularized peritoneal matrix to study therapy response
Abstract High-grade serous ovarian carcinoma (HGSOC) presents a significant therapeutic challenge. Late-stage disease is frequently associated with peritoneal carcinomatosis. The peritoneal metastases exhibit a unique tumor microenvironment (TME) distinct from the primary tumors and other metastatic sites. Understanding the critical influence of the extracellular matrix (ECM) in shaping the tumor phenotype is essential for the development of effective new therapies. This study introduces a novel three-dimensional (3D) model of HGSOC peritoneal metastases using a porcine decellularized peritoneal-derived ECM scaffold, referred to as peritoneal matrix (PerMa). We show that the decellularization maintains the structural integrity and composition of ECM molecules. Comparative analysis reveals structural, compositional, and mechanical similarities between porcine and human peritoneal matrices, underscoring the porcine model’s translational relevance for modeling human peritoneum physiology. The PerMa supports the 3D growth of HGSOC cell lines. The model enables the assessment of sensitivity to traditional chemotherapy and novel cell-based immunotherapy through confocal imaging and quantification of cell volume. Our model offers a valuable platform for investigating peritoneal carcinomatosis in HGSOC, with the potential to contribute significantly to the development of novel therapeutic approaches.
2024-05-06 | Creation and Validation of Patient-Derived Cancer Model Using Peritoneal and Pleural Effusion in Patients with Advanced Ovarian Cancer: An Early Experience
Background: The application of personalized cancer treatment based on genetic information and surgical samples has begun in the field of cancer medicine. However, a biopsy may be painful for patients with advanced diseases that do not qualify for surgical resection. Patient-derived xenografts (PDXs) are cancer models in which patient samples are transplanted into immunodeficient mice. PDXs are expected to be useful for personalized medicine. The aim of this study was to establish a PDX from body fluid (PDX-BF), such as peritoneal and pleural effusion samples, to provide personalized medicine without surgery. Methods: PDXs-BF were created from patients with ovarian cancer who had positive cytology findings based on peritoneal and pleural effusion samples. PDXs were also prepared from each primary tumor. The pathological findings based on immunohistochemistry were compared between the primary tumor, PDX, and PDX-BF. Further, genomic profiles and gene expression were evaluated using DNA and RNA sequencing to compare primary tumors, PDXs, and PDX-BF. Results: Among the 15 patients, PDX-BF was established for 8 patients (5 high-grade serous carcinoma, 1 carcinosarcoma, 1 low-grade serous carcinoma, and 1 clear cell carcinoma); the success rate was 53%. Histologically, PDXs-BF have features similar to those of primary tumors and PDXs. In particular, PDXs-BF had similar gene mutations and expression patterns to primary tumors and PDXs. Conclusions: PDX-BF reproduced primary tumors in terms of pathological features and genomic profiles, including gene mutation and expression. Thus, PDX-BF may be a potential alternative to surgical resection for patients with advanced disease.
2022-09-20 | IL12 immune therapy clinical trial review: Novel strategies for avoiding CRS-associated cytokines
Interleukin 12 (IL-12) is a naturally occurring cytokine that plays a key role in inducing antitumor immune responses, including induction of antitumor immune memory. Currently, no IL-12-based therapeutic products have been approved for clinical application because of its toxicities. On the basis of this review of clinical trials using primarily wild-type IL-12 and different delivery methods, we conclude that the safe utilization of IL-12 is highly dependent on the tumor-specific localization of IL-12 post administration. In this regard, we have developed a cell membrane-anchored and tumor-targeted IL-12-T (attIL12-T) cell product for avoiding toxicity from both IL-12 and T cells-induced cytokine release syndrome in peripheral tissues. A phase I trial using this product which seeks to avoid systemic toxicity and boost antitumor efficacy is on the horizon. Of note, this product also boosts the impact of CAR-T or TCR-T cell efficacy against solid tumors, providing an alternative approach to utilize CAR-T to overcome tumor resistance.
other
2026-04-08 | Engineered Oncolytic Vaccinia Virus Strategies for High-Grade Serous Carcinoma: Intraoperative Visualisation and Autoimmune Redirection
Background: High-grade serous carcinoma (HGSC) accounts for 70–80% of ovarian cancermortality, with five-year survival for advanced disease below 25%. Immune checkpointinhibitors have failed in this indication (objective response rates 10–15%), and no oncolyticvirus is approved for ovarian cancer. Two critical unmet needs persist: incomplete surgicalcytoreduction due to the inability to detect occult peritoneal disease invisible to standardwhite-light inspection, and the absence of effective immunotherapy. Methods: Two novel oncolytic virus therapeutic concepts were developed throughsystematic review of the published clinical and preclinical literature, consultation withpractising clinicians, and structured analytical interrogation using a multi-source triangulationmethodology designed to identify consensus findings and surface areas of genuine scientificuncertainty. All conclusions were verified against primary sources. Concept 1 (Intraoperative Visualisation): A replication-competent vaccinia virus armedwith near-infrared fluorescent protein (iRFP713) and melanogenic enzymes(tyrosinase/TYRP1) to make residual HGSC deposits visible during cytoreductive surgery.Unlike passively administered fluorescent dyes, the replicating virus self-amplifiesthroughout the peritoneal tumour burden, providing four independent detection channels(NIR fluorescence, naked-eye melanin pigmentation, MRI contrast, photoacoustic imaging)from a compact ~4.2 kb payload using only 21% of the viral insertion capacity. Concept 2 (Autoimmune Redirection): A replication-competent vaccinia virus expressingthyroid autoantigens (thyroperoxidase and thyroglobulin) with immunostimulatory copayloadsto redirect pre-existing Hashimoto’s thyroiditis autoimmunity against HGSC tumourcells in the up to 10% of HGSC patients with coexisting autoimmune thyroid disease. Results: Vaccinia virus was identified as the optimal platform based on unmatchedtransgene capacity (~25 kb), established HGSC clinical data (Olvi-Vec Phase II/III), validatedintraperitoneal delivery, and existing safety infrastructure. The immunologically cold HGSCmicroenvironment, typically a barrier to immunotherapy, was identified as strategicallyadvantageous for both concepts. A dual-territory development strategy is proposed: Concept1 via Western (FDA) pathway first; Concept 2 via China-first development to exploit higherHashimoto’s prevalence in East Asian populations, with both territories pursued in parallel. Conclusions: Both concepts integrate proven, published technologies into novelcombinatorial architectures addressing distinct unmet needs in HGSC. Concept 1 offers alower-risk pathway to improving surgical outcomes; Concept 2 offers potentially curativeimmunotherapy for a defined patient subset. Both are built on a shared vaccinia backbone,enabling a single manufacturing programme.
2026-02-07 | Pembrolizumab and epigenetic modification with azacitidine reshapes the tumor microenvironment of platinum-resistant epithelial ovarian cancer: a phase 2 non-randomized clinical trial.
Epigenetic modulators may sensitize platinum-resistant ovarian cancer (PROC) to immune checkpoint inhibition by reprogramming the tumor microenvironment. We report clinical and translational findings from a phase II non-randomized study of pembrolizumab and oral azacitidine in 34 women with PROC (NCT02900560). Key eligibility criteria included age 18 years or older, performance status of 0-1, measurable disease, platinum-resistant disease and histologically confirmed epithelial ovarian cancer, fallopian tube carcinoma or primary peritoneal carcinoma. Primary endpoints included safety, tolerability, overall response rate (ORR) and disease control rate (DCR). Secondary endpoints included CA-125 response. The effect of combined epigenetic and immunotherapy was evaluated by transcriptomic analyses of 72 serially biopsied tumors. We show that the combination is moderately well tolerated and most common grade 3-4 adverse events are gastrointestinal side effects and anemia. ORR is 2.9% and DCR is 50%; with 3 of the 27 evaluable patients attaining a CA-125 response. Differential gene expression analyses reveal an upregulation of inflammatory and cytolytic genes and co-inhibitory checkpoints 6 weeks on-therapy. Upregulation of interferon signaling, antigen presentation and immune cell adhesion and migration gene sets are prominent on-therapy, together with an increase in density of CD8 + T-cells. Patients with a CA-125 and/or clinical response show an enrichment of adaptive and conserved immune response gene sets on-therapy. Our findings highlight the potential of epigenetic modulators to re-shape the tumor microenvironment of PROC toward a more inflammed phenotype and may point to approaches to augment immunotherapy response.
2025-12-12 | Safety and feasibility of talimogene laherparepvec in peritoneal surface malignancies: Results from the TEMPO trial
Peritoneal surface malignancies (PSMs) remain a therapeutic challenge, particularly in patients with unresectable disease who cannot benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. The Talimogene Laherparepvec for the Treatment of Peritoneal Surface Malignancies (TEMPO) trial (NCT03663712) is the first phase 1, multicenter, open-label study to evaluate intraperitoneal (i.p.) administration of talimogene laherparepvec (T-VEC), an FDA-approved oncolytic virus, in this setting. Nineteen patients with unresectable PSMs from appendiceal, ovarian, small bowel, and peritoneal carcinomas were enrolled; 18 received treatment across three escalating dose cohorts (4 × 106-4×108 PFU). The primary endpoint was safety and tolerability, with secondary endpoints assessing viral kinetics and shedding, and an exploratory efficacy endpoint. T-VEC demonstrated a manageable safety profile, with gastrointestinal and systemic toxicities more frequent at higher doses but no dose-limiting toxicities; one case of grade 3 neutropenia was observed. Herpes simplex virus 1 (HSV-1) DNA exhibited a dose-dependent persistence pattern, peaking later in higher dose cohorts, while plasma and urine remained consistently negative, supporting biosafety. Clinically, one complete response and ten cases of stable disease (4-19 months) were observed, while six patients experienced progression. These findings establish the safety and feasibility of i.p. T-VEC for unresectable PSMs, demonstrate localized viral replication without systemic dissemination, and suggest preliminary signals of clinical activity warranting further investigation in larger, more diverse cohorts.
2025-05-28 | Phase I study of oncolytic adenovirus BioTTT001 in patients with peritoneal carcinomatosis.
e14553 Background: The prognosis of secondary peritoneal carcinoma with malignant ascites（MA）is poor, highlighting the urgent need for new therapeutic regime. BioTTT001 is a novel oncolytic adenovirus (Ad) expressing a mutant form of interleukin-12, based on a new generation of tumor-targeted replicating oncolytic Ad backbone of human Ad5 by deleting E1A CR2 domain, E1B19K , and E3gp19K while keeping E3B genes of Ad intact. Here we report the results of the first-in-human Phase I clinical trial of BioTTT001 for the treatment of peritoneal metastasis. Methods: It's a dose-escalation, single-center clinical trial. Eligible patients (pts) had histopathologically confirmed refractory secondary peritoneal carcinomatosis from solid tumors, including gastric, colorectal and ovarian cancers. Dose escalation follows a 3+3 design at 3 dose levels. BioTTT001 is administered via intraperitoneal perfusion on days 1,3, and 5 in the first week, followed by weekly dosing for a total of 21 days per cycle. The primary endpoints include the Maximal Tolerable Dose / Recommended Phase 2 Dose (RP2D) and the incidence of adverse events. Secondary endpoints encompass preliminary clinical efficacy such as objective response rate, disease control rate (DCR), and changes in ascites volume assessed using the five-point method (5PM). The pharmacokinetics, pharmacodynamics characteristics of BioTTT001 and host immune responses to the virus were investigated as well. Results: As of Sep 30, 2024, nine pts were enrolled and received BioTTT001 intraperitoneal monotherapy (3 pts in cohort 5×10 9 vp, 3 pts in cohort 5×10 10 vp, 3 pts in cohort 1×10 10 vp). 5 pts had primary gastric cancer, 3 had ovarian cancer and 1 had rectal cancer. No DLTs were reported. Most treatment-related adverse events (TRAEs) were classified as grade 1-2; grade≥3 TRAEs including fatigue (22%), abdominal pain (11%) and lymphopenia (22%), occurred in 3/9 (33%) pts. The most common TRAEs were transient abdominal pain and fever following the virus administration. RP2D was identified as 1×10 10 vp. DCR reached 100% (5/5) among pts with measurable disease at baseline, while a reduction rate of ascites was noted at 80% (4/5) among evaluable subjects based on the 5PM. Additionally, CA125 levels decreased in 4/9 pts ( > 40% decrease observed in 2 pts). Notably, 2 pts with pelvic peritoneal metastasis exhibited significant regression of both pelvic metastases and adjacent intestinal lesions following the treatment. PCR analysis of ascites from 6 pts showed that BioTTT001 persisted in the peritoneal cavity (PC) for one week. Of note, BioTTT001 could result ineffective recruitment of CD8 + T and NK cells in PC. Conclusions: The intraperitoneal infusion of BioTTT001 for the treatment of peritoneal metastatic cancer was well tolerated with encouraging clinical benefit in pelvic peritoneal metastasis and MA controlling. This warrants further clinical investigation. Clinical trial information: ChiCTR2300069323 .
2025-05-13 | Human Papillomaviruses and Malignant Neoplasms of the Female Upper Reproductive Tract: A Comprehensive Review of the Literature
Malignancies of the female upper reproductive tract, especially endometrial and ovarian cancers, consist a significant burden for women worldwide. The possible etiopathogenetic role of chronic human papillomavirus (HPV) infection in the female upper genital tract carcinogenesis is neither clearly established not completely understood. Therefore, we performed a literature review through PubMed and SCOPUS electronic databases about the prevalence of HPV DNA in endometrial, primary fallopian tube, ovarian and primary peritoneal cancers, as well as uterine sarcomas. The present investigation covered 35 studies from different countries of various continents. Overall, HPV prevalence was approximately 15% in all the above cancers. HPV DNA was isolated from 11%, 0%, 0% and 14% of endometrial carcinomas, uterine sarcomas, primary fallopian tube cancers and ovarian malignant neoplasms, respectively. No relevant studies on primary peritoneal cancers were retrieved. The predominant HPV strain from all tumors of the upper female reproductive tract, regardless of the tumor site, was mostly HPV-16, followed by HPV-18. HPV DNA was identified exclusively from subtypes HPV-6, HPV-11, HPV-16, HPV-18, and HPV-33, which are responsible for the development of not only cervical cancer, but also of condylomata acuminata. The findings of the present review indicate that HPV vaccination might prove to be a useful strategy in the prevention HPV-related carcinomas of the upper genital tract in women.
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Drug Discovery Landscape
7 orphan drug designations for Primary peritoneal carcinoma, including 2 approved therapies.
7 orphan drug designations for Primary peritoneal carcinoma, including 2 approved therapies.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Gleolan | small molecules | FDA | NX Development Corp. | |
olaparib [Lynparza] | small molecules | FDA | Approved | AstraZeneca Pharmaceuticals LP |
antibody drug conjugate targeting dipeptidase 3 (DPEP3) | antibodies | FDA | AbbVie Stemcentrx, LLC | |
pelareorep | gene therapies | FDA | Oncolytics Biotech, Inc. | |
bevacizumab [Avastin] | antibodies | FDA | Approved | Genentech, Inc. |
patupilone | small molecules | FDA | Novartis Pharmaceuticals Corporation | |
Patupilone | small molecules | EMA | Novartis Europharm Limited |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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