RARE DISEASE
Adenocarcinoma of ovary
Adenocarcinoma of ovary
Adenocarcinoma of ovary
Synonyms: Ovarian adenocarcinoma
Synonyms: Ovarian adenocarcinoma
Synonyms: Ovarian adenocarcinoma
Drug discovery
1
drug
With orphan designation
Overview
Ovarian adenocarcinoma, the most common epithelial ovarian cancer, arises from Müllerian epithelium and includes high-grade serous (most prevalent), endometrioid, clear cell, and mucinous subtypes [1][5]. Typically diagnosed at advanced stages (III/IV) due to nonspecific symptoms, it demonstrates varying chemosensitivity – clear cell and mucinous subtypes show particular resistance to platinum-based regimens [1][4][7]. Prognosis remains poor with 46% 5-year survival overall, dropping below 30% in advanced disease [4][10].
Categories: rare gynecological and obstetric diseases, rare neoplastic diseases
Research Papers
2,472 drug discovery papers about Adenocarcinoma of ovary, with 2 first-in-class and 8 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2,472 drug discovery papers about Adenocarcinoma of ovary, with 2 first-in-class and 8 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-17 | Design, Synthesis, and Evaluation of Alkoxyamine Anticancer Prodrugs Bearing Galactoside as an Enzyme-Activated Trigger.
Enzyme-induced cytotoxicity can be considered the main challenge in modern cancer therapy that provides unique opportunities for targeted apoptosis. To address this challenge, we implemented enzyme-triggered activation of alkoxyamine-galactose conjugates with the formation of active carbon-centered radical species for the apoptosis of cancer cells. The comparative analysis of two alkoxyamine derivatives, bearing stable and self-immolative linkers between the radical precursor and galactose moiety, revealed the crucial role of molecular structure in anticancer activity. The study of cytotoxicity and induced oxidative stress of free amine and two galactosides revealed the enzyme-dependent nature of the activity of alkoxyamines having a self-immolative linker against distinct cancer cell lines such as PC-3 (prostate adenocarcinoma), SKOV-3 (ovarian adenocarcinoma), MCF-7 (breast adenocarcinoma), A-431 (epidermoid carcinoma), and Jurkat cells (human T-lymphoblastic leukemia). The collected data prove the applicability of enzyme-triggered glycosylated alkoxyamines as a new family of targeted prodrugs against cancer.
2026-07-16 | Anticancer potential of β-isopropylfuran-1,2-naphthoquinone in different types of tumor cell lines.
Cancer is a multifactorial disease characterized by uncontrolled cell growth and remains a major global health challenge. Given the limitations of conventional therapies, naturally derived compounds such as naphthoquinones have attracted interest for their antitumor potential. This study evaluated the in vitro effects of β-isopropylfuran-1,2-naphthoquinone (NAF-Q69), a synthetic isolapachol derivative, on different cell lines (MRC-5 - human lung fibroblasts; HEPG2 - hepatocellular carcinoma; HeLa - cervical cancer; TOV - ovarian adenocarcinoma; MDA-MB - breast adenocarcinoma; and J82 - urothelial carcinoma) to assess its cytotoxic activity and cellular characteristics (clonogenic survival, migration, morphology, cell cycle, and reactive oxygen species \[ROS] production). NAF-Q69 showed significant dose-dependent cytotoxicity in all tumor lines, with IC50 values ranging from 10.29 µM (MDA-MB) to 18.65 µM (HEPG2). It decreased viability, inhibited colony formation, and impaired migration, particularly in TOV, HeLa, and HEPG2 cells. Morphological alterations were evident. The compound induced cell death, with increased sub-G1 populations, and promoted G2/M arrest. Moreover, NAF-Q69 markedly elevated ROS levels, implicating oxidative stress as a central mechanism. In conclusion, NAF-Q69 exhibits promising antitumor activity by inhibiting proliferation and migration, inducing cell death, and enhancing oxidative stress, supporting the potential of naphthoquinones in cancer therapy.
2026-06-06 | Overexpression of scavenger receptor class B member 2 leads to different response of ovarian adenocarcinoma cells to chemotherapy.
Scavenger Receptor Class B Member 2 (SCARB2) is an integral lysosomal membrane protein essential for lysosomal integrity and autophagy regulation. The aim of this study was to investigate the functional impact of SCARB2 overexpression on chemotherapy response, reactive oxygen species (ROS) production and proteomic composition of human ovarian adenocarcinoma cells A2780. To induce SCARB2 overexpression, A2780 cells were transfected using a PiggyBac vector system. Two clones with the highest SCARB2 expression (L and V) were selected for further analyses. Differences in chemosensitivity were assessed using the MTS assay. Proteomic analysis was used to identify differentially expressed proteins and enriched pathways. We also performed flow cytometry to investigate changes in ROS production and lysosomal activity. Lysosomal distribution was assessed using LAMP1 immunofluorescence staining followed by confocal microscopy, and total cholesterol levels were determined using an enzymatic colorimetric assay. Both clones showed increased sensitivity to cisplatin compared to the control group. In contrast, clone V showed resistance to doxorubicin and no significant differences were observed for gemcitabine, except for a transient sensitizing effect when low concentrations used. Elevated ROS levels were detected in untreated clones, and after doxorubicin exposition. Proteomic analysis showed significant changes in lysosome-associated proteins, with consistent enrichment of the lysosomal pathway across all experimental comparisons. Immunofluorescence analysis of LAMP1 and LysoTracker staining demonstrated altered lysosomal distribution and activity in SCARB2-overexpressing clones. In addition, both SCARB2-overexpressing clones exhibited significantly reduced total cholesterol levels compared with control cells. This study broadens our understanding of SCARB2 in ovarian cancer. SCARB2 overexpression induces extensive lysosomal reprogramming in A2780 ovarian cancer cells and modulates chemotherapy response.
2026-05-01 | Punicalagin Inhibits the Growth and Proliferation of Ovarian Epithelial Adenocarcinoma Cells Via Apoptosis and Autophagic Cell Death
Ovarian cancer remains a leading cause of gynecologic cancer-related mortality and is frequently associated with therapeutic resistance. Punicalagin (PCG), a pomegranate-derived polyphenol, has demonstrated anticancer activity in multiple tumor models, however, its effects in ovarian cancer require further clarification. This study evaluated the anti-proliferative and anti-migratory effects of PCG in two biologically distinct ovarian cancer cell lines, OVCAR-3 and SKOV-3. PCG treatment (6.25-200 µM) significantly reduced cell viability and colony formation in a dose- and time-dependent manner. Migration-associated behaviors were suppressed in wound-healing and transwell assays, accompanied by modulation of epithelial-mesenchymal transition markers, including increased E-cadherin and decreased N-cadherin expression. PCG increased reactive oxygen species (ROS) levels and reduced mitochondrial membrane potential in both cell lines. Annexin V/propidium iodide analysis demonstrated increased apoptotic cell populations, with elevated BAX expression. Autophagy-related changes, including LC3-I to LC3-II conversion and acridine orange-positive vesicles, were observed in OVCAR-3 cells but not in SKOV-3 cells. Collectively, these findings indicate that PCG exerts anti-proliferative and pro-apoptotic effects in ovarian cancer cells and is associated with oxidative stress and mitochondrial dysfunction. Further studies are required to define the mechanistic contribution of ROS and autophagy and to evaluate translational relevance in vivo.
2026-04-13 | Organoids serve as viable in vitro model for functional precision medicine for mesonephric-like adenocarcinoma of the ovary
Abstract Background Mesonephric-like adenocarcinoma has been recently classified as a rare type of ovarian carcinoma. Description of these tumours have been rare and mostly covered in case reports. In some cases, molecular characterization by sequencing has been employed for guided therapy recommendations, however, functional chemosensitivity testing of targetable pathways using advanced in vitro cellular models such as organoids has not been reported so far. Here, we report on a case of ovarian cancer that was later identified as mesonephric-like adenocarcinoma at an advanced stage. Methods The tumour was characterized by molecular techniques including immunohistochemistry and whole-exome sequencing. At the same time, ovarian cancer organoids were established by adapting existing protocols for high-grade serous ovarian carcinoma. The organoids were subsequently used for functional in vitro chemosensitivity testing by treatment with standard-of-care chemotherapeutics cisplatin, paclitaxel, and the Poly (ADP-Ribose) Polymerase 1-inhibitor olaparib. Based on molecular characteristics, we also applied the inhibitor binimetinib, to target Mitogen-Activated Protein Kinase downstream of the KRAS Proto-Oncogene. Additionally, chemotoxicity testing with healthy fallopian tube organoids and high-grade ovarian cancer organoids was applied to determine the therapeutic window. Results Immunohistochemical analysis showed characteristic PAX8 + , GATA3 + , TFF1 + , ER - , PR - , WT1 - staining while the sequencing revealed mutations in 31 genes of which KRAS G12V and DYNC1H1 G4072S were annotated as (likely) pathogenic. The tumour was mismatch-repair proficient. Tumour-derived organoids proved to be highly resistant to standard-of-care chemotherapeutics cisplatin, paclitaxel, and olaparib, but sensitive to inhibition by binimetinib, which aligned well with the molecular characteristics. Direct comparison to healthy fallopian tube organoids and high-grade ovarian cancer organoids confirmed low cytotoxic potential underlining a feasible therapeutic window for binimetinib. Conclusions For the first time, we show that existing protocols for high-grade serous ovarian carcinoma can be used for the generation of organoids derived from mesonephric-like adenocarcinoma. These organoids could be used as an essential tool for functional precision medicine purposes. This functional data could be applied as an additional layer for molecular tumour boards diagnostics by supporting molecular datasets and even identify targetable pathways beyond genetic variations, thus offering novel therapeutic options particularly for rare and aggressive tumours.
proteins
2026-01-26 | Overexpression of biliverdin reductase A leads to ROS-independent sensitization of ovarian adenocarcinoma cells to gemcitabine.
Biliverdin reductase A (BLVRA) is a key enzyme in bilirubin metabolism, where it reduces biliverdin to bilirubin. Bilirubin is a potent antioxidant that protects cells from oxidative stress. Therefore, reduced or deregulated BLVRA activity may contribute to increased oxidative DNA damage, which is one of the factors leading to the neoplastic transformation of cells. Human ovarian adenocarcinoma A2780 cells were transfected with a PiggyBac vector to achieve BLVRA overexpression. A2780 clones showing the most significant BLVRA gene overexpression were analyzed by proteomics and flow cytometry to assess rective oxygen species (ROS) production. Our results indicate that BLVRA overexpression increases the sensitivity of A2780 cells to doxorubicin and gemcitabine, with the most pronounced effect observed in the J clone. In this clone, the highest level of BLVRA overexpression correlated with significant alterations in the p53 signaling pathway. Upregulation of key effectors such as Bax and CDKN2A indicates a potential role for BLVRA in promoting pro-apoptotic responses. Moreover, BLVRA overexpression increased the sensitivity of A2780 cells to gemcitabine independently of ROS. This study broadens our understanding of BLVRA in ovarian cancer. In cells with intact p53 signaling, BLVRA overexpression can paradoxically enhance cytotoxic response to certain drugs, particularly gemcitabine.
2025-07-31 | Ultrabright NIR-II Nanoprobes for Ex Vivo Bioimaging: Protein Nanoengineering Meets Molecular Engineering
ABSTRACT Near-infrared (NIR) fluorescence imaging is a powerful, non-invasive tool for cancer diagnosis, enabling real-time, high-resolution visualization of biological systems. While most probes target the first NIR window (NIR-I, 750-950 nm), recent advances focus on the second window (NIR-II, 1000-1700 nm), which offers deeper tissue penetration and reduced interferences from scattering and autofluorescence. However, many current NIR-II nanoprobes show suboptimal brightness and limited validations in more human-centric models. Here, we present an orthogonal strategy combining molecular engineering, by modulating the amount and position of thiophene moieties in semiconducting polymers (SPs), with protein nanoengineering to develop ultrabright NIR-II imaging probes optimized for ex vivo bioimaging in large animal models. The molecular tuning amplifies the NIR-II fluorescence brightness while screening endogenous proteins as encapsulating matrices to improve colloidal stability and enable active targeting. Molecular docking identified bovine serum albumin as the effective candidate, and the resulting protein-complexed nanoprobes were characterized for size, colloidal stability under physiological conditions, and optical performances. Imaging performances were evaluated using tumor-mimicking phantoms in porcine lungs, simulating cancer surgery, and injected at clinically relevant concentrations into ovine brains and porcine ovaries for microvascular visualization and tissue discrimination, respectively. In all scenarios, our protein-complexed nanoprobes outperformed the FDA-approved clinical dye indocyanine green in signal-to-background ratios. Initial in vitro assays confirmed their hemocompatibility, biocompatibility, and cellular uptake in ovarian adenocarcinoma cells. This integrated approach offers a promising platform for developing next-generation ultrabright NIR-II nanoprobes with improved brightness and stability, advancing the potential for image-guided surgery and future clinical translation. Abstract Figure
2024-08-22 | The first-in-class pro-apoptotic peptide PEP-010 is effective in monotherapy and in combination with paclitaxel on resistant ovarian adenocarcinoma cell models.
Ovarian adenocarcinoma is the gynecological malignancy with the worst prognosis and the highest mortality rate. In the first stages of treatment, chemotherapy results effective, but its prolonged use and high doses lead to the appearance of resistance to treatments and relapse in most patients, representing a major challenge for clinicians. We developed PEP-010, a cell penetrating proapoptotic peptide disrupting the protein-protein interaction between caspase-9 and protein phosphatase 2A, thereby leading to the recovery of their activity in the apoptotic pathway. MTT assay or Annexin-V/Propidium Iodide staining and flow cytometry analysis were used to assess sensitivity to chemotherapies and apoptosis after treatment with PEP-010 in monotherapy or in combination with paclitaxel in ovarian carcinoma cell lines. DNA damage was assessed by immunofluorescence using γH2AX marker. We show here that PEP-010 effectively induces cell death in monotherapy on in up to 55% of cells from ovarian adenocarcinoma cell models resistant to different chemotherapies. Moreover, when used in combination with paclitaxel, one of the therapeutic options for recurrent ovarian carcinoma, PEP-010 showed a beneficial effect leading to the reduction of the IC50 of paclitaxel of 2.2 times and to apoptosis in 87% of cells. The described results suggest the potential therapeutic interest for PEP-010 and lead to the choice of ovarian adenocarcinoma as one of the major indications of the ongoing clinical trial.
2024-06-01 | A phase I open-label study of a novel IL-2Rβ/γ cytokine agonist, LTC004, in patients with advanced or metastatic solid tumors.
2652 Background: LTC004, a novel IL-2Rβ/γ cytokine agonist, designed to minimize toxicity with improved potency. It has selective affinity for the receptor IL-2Rβγ subunits, preferentially stimulates CD8 + effector T cells and natural killer cells which are associated with tumor killing, while minimizing the activation of immunosuppressive regulatory T cells. LTC004 has shown significant in vitro and in vivo anti-tumor activity in multiple cell lines and murine models respectively. Methods: This is a first-in-human, multicenter, open-label, dose-escalation and dose-expansion phase I study of LTC004 in advanced solid tumors. Dose escalation part assessed safety and tolerability of intravenous LTC004 with doses ranging from 3.0 to 360 µg/kg. The dose escalation schedule utilized an accelerated titration and Bayesian Optimal Interval (BOIN) design. Eligible pts with advanced solid tumor were required to have received prior standard therapy. LTC004 is administrated intravenously once every 3 weeks. Results: The study completed dose-escalation part (3.0 to 360 µg/kg) as of cutoff date (Jan 10, 2024). 17 pts of multiple tumor types (including non-small cell lung, cervical, colorectal, sarcoma, melanoma, parotid adenocarcinoma, thymic adenocarcinoma, gastric and ovarian cancers) were enrolled and received ≥1 dose of LTC004. At baseline, 12 pts (70.6%) had received ≥2 prior lines therapy, 11 pts (64.7%) had received prior targeted therapy, 10 pts (58.8%) had received prior immune checkpoint inhibitor (ICI) therapy. LTC004 generally well tolerated and no dose-limiting toxicities (DLTs) up to and including 360 µg/kg was observed. The most common TEAEs overall in ≥30% of pts were fever, white blood cell decreased, anemia, AST/ALT increased, neutrophil count decreased, GGT increased, nausea and hypotension. Most of the reported AEs were G1 and G2, all drug related events reversible and responsive to supportive care therapy. Fever can be resolved with standard anti-pyretic treatment or steroids, transient hypotension can be preventable with prophylactic fluid infusion. Of 17 pts enrolled evaluable for efficacy per RECIST v1.1, the ORR were 5.9% (1/17), DCR were 58.8% (10/17). A confirmed PR was achieved in a pMMR/MSS CRC patient with prior therapies including fluoropyrimidines, irinotecan, oxaliplatin, targeted therapy and TKI. The starting dose was 45µg/kg, titration to 90µg/kg after 4 consecutive doses at 45µg/kg Q3W. As of cutoff date, the patient sustained PR for 4.8 months with follow-up ongoing. Conclusions: LTC004 demonstrated encouraging anti-tumor efficacy including cold tumor, and well tolerated in patients with advanced or metastatic solid tumors. The further dose expansion in selected tumor types is ongoing, and evaluations in combination with other agents are being planned. Clinical trial information: NCT05666635 .
2024-02-01 | RGD peptide in cancer targeting: Benefits, challenges, solutions, and possible integrin-RGD interactions.
Abstract RGD peptide can be found in cell adhesion and signaling proteins, such as fibronectin, vitronectin, and fibrinogen. RGD peptides' principal function is to facilitate cell adhesion by interacting with integrin receptors on the cell surface. They have been intensively researched for use in biotechnology and medicine, including incorporation into biomaterials, conjugation to medicinal molecules or nanoparticles, and labeling with imaging agents. RGD peptides can be utilized to specifically target cancer cells and the tumor vasculature by engaging with these integrins, improving drug delivery efficiency and minimizing adverse effects on healthy tissues. RGD‐functionalized drug carriers are a viable option for cancer therapy as this focused approach has demonstrated promise in the future. Writing a review on the RGD peptide can significantly influence how drugs are developed in the future by improving our understanding of the peptide, finding knowledge gaps, fostering innovation, and making drug design easier.
antibodies
2026-07-21 | Abstract A005: VBC106: A First-in-class FOLR1/MSLN Targeted Tri-specific Antibody Drug Conjugate (ADC) in Ovarian Cancer, Endometrial Cancer, Lung Adenocarcinoma and Beyond
Abstract FOLR1 and MSLN are GPI-anchored proteins involved in cancer pathogenesis. The therapeutic potential of targeting FOLR1 is demonstrated by the approval of Elahere (mirvetuximab soravtansine-gynx; IMGN853). However, Elahere selects patients with FOLR1 high expression (TPS≥75), and poses safety concern of severe ocular toxicities. Recently, RC88 showed preliminary efficacy in patients with IHC 2+ or higher MSLN expression, highlighting MSLN as a potential therapeutic target. Despite this, unmet needs remain for patients with low FOLR1 or MSLN expression. Notably, FOLR1 and MSLN are highly co-expressed in solid tumors like ovarian cancer, endometrial cancer, lung adenocarcinoma and so on, but limited in normal tissues, offering an opportunity for tumor-specific targeting and supporting bispecific designs. VBC106 is a tri-specific antibody-drug conjugate (ADC) targeting both FOLR1 and MSLN. It delivers a TOPOi payload with a strong bystander effect, maximizing efficacy while minimizing safety concerns. VBC106 distinguishes itself from other drugs targeting FOLR1 and/or MSLN with the following features: Optimized Structure: VBC106 has a high-avidity bi-paratopic FOLR1 arm and a high-affinity MSLN arm, the structure was optimized to enhance synergistic binding and achieve maximum internalization. High in-vitro Potency: VBC106 demonstrates stronger cytotoxicity and a more potent bystander effect than Elahere analogues and PRO1184. Superior in-vivo Efficacy in CDX: In over 10 CDX models of various cancer types, VBC106 showed superior efficacy compared to Elahere analogues and PRO1184. And it is effective in FOLR1 low-expression models where others are not. High Response Rate in PDX: VBC106 shows a high response rate in PDX models across multiple cancer types. Good Pharmacokinetics: In NHP, VBC106 has a half-life of about 4 days. Large Therapeutic Window: GLP toxicity studies in cynomolgus monkeys indicate good tolerability at repeated doses. The HNSTD is 40 mg/kg. In summary, VBC106, with its unique tri-specific design and differentiated features, has superior efficacy and high safety, making it a promising first-in-class ADC candidate for clinical development, with a U.S. IND submission planned for Q2 2026. Citation Format: Man Xu, Xuekun Zhang, Wei Wang, Kevin Yin, Yajun Huang, Yanling Gong, Yingchun Wang, Jing Li. VBC106: A First-in-class FOLR1/MSLN Targeted Tri-specific Antibody Drug Conjugate (ADC) in Ovarian Cancer, Endometrial Cancer, Lung Adenocarcinoma and Beyond [abstract]. In: Proceedings of AACR Drug Discovery and Development (AACR D3) Conference; 2026 Jul 21-24; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(14_Suppl):Abstract nr A005.
2026-07-21 | Abstract PR008: VBC106: A First-in-class FOLR1/MSLN Targeted Tri-specific Antibody Drug Conjugate (ADC) in Ovarian Cancer, Endometrial Cancer, Lung Adenocarcinoma and Beyond
Abstract FOLR1 and MSLN are GPI-anchored proteins involved in cancer pathogenesis. The therapeutic potential of targeting FOLR1 is demonstrated by the approval of Elahere (mirvetuximab soravtansine-gynx; IMGN853). However, Elahere selects patients with FOLR1 high expression (TPS≥75), and poses safety concern of severe ocular toxicities. Recently, RC88 showed preliminary efficacy in patients with IHC 2+ or higher MSLN expression, highlighting MSLN as a potential therapeutic target. Despite this, unmet needs remain for patients with low FOLR1 or MSLN expression. Notably, FOLR1 and MSLN are highly co-expressed in solid tumors like ovarian cancer, endometrial cancer, lung adenocarcinoma and so on, but limited in normal tissues, offering an opportunity for tumor-specific targeting and supporting bispecific designs. VBC106 is a tri-specific antibody-drug conjugate (ADC) targeting both FOLR1 and MSLN. It delivers a TOPOi payload with a strong bystander effect, maximizing efficacy while minimizing safety concerns. VBC106 distinguishes itself from other drugs targeting FOLR1 and/or MSLN with the following features: Optimized Structure: VBC106 has a high-avidity bi-paratopic FOLR1 arm and a high-affinity MSLN arm, the structure was optimized to enhance synergistic binding and achieve maximum internalization. High in-vitro Potency: VBC106 demonstrates stronger cytotoxicity and a more potent bystander effect than Elahere analogues and PRO1184. Superior in-vivo Efficacy in CDX: In over 10 CDX models of various cancer types, VBC106 showed superior efficacy compared to Elahere analogues and PRO1184. And it is effective in FOLR1 low-expression models where others are not. High Response Rate in PDX: VBC106 shows a high response rate in PDX models across multiple cancer types. Good Pharmacokinetics: In NHP, VBC106 has a half-life of about 4 days. Large Therapeutic Window: GLP toxicity studies in cynomolgus monkeys indicate good tolerability at repeated doses. The HNSTD is 40 mg/kg. In summary, VBC106, with its unique tri-specific design and differentiated features, has superior efficacy and high safety, making it a promising first-in-class ADC candidate for clinical development, with a U.S. IND submission planned for Q2 2026. Citation Format: Man Xu, Xuekun Zhang, Wei Wang, Kevin Yin, Yajun Huang, Yanling Gong, Yingchun Wang, Jing Li. VBC106: A First-in-class FOLR1/MSLN Targeted Tri-specific Antibody Drug Conjugate (ADC) in Ovarian Cancer, Endometrial Cancer, Lung Adenocarcinoma and Beyond [abstract]. In: Proceedings of AACR Drug Discovery and Development (AACR D3) Conference; 2026 Jul 21-24; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(14_Suppl):Abstract nr PR008.
2026-07-01 | Complete Remission of Erythrodermic Psoriasis After Bevacizumab Administration for Ovarian Serous Adenocarcinoma: A Case Report
ABSTRACT Patients who have both erythrodermic psoriasis and advanced ovarian cancer are uncommon in clinical practice. This case study presents the case of a patient diagnosed with erythrodermic psoriasis for a duration exceeding 4 years. The patient was administered ixekizumab and adalimumab, but no remission was observed during the illness. The patient was diagnosed with metastatic ovarian serous adenocarcinoma involving multiple lymph nodes and liver in 2022. During her bevacizumab treatment, she experienced a complete remission of psoriasis without any other management for psoriasis.
2026-06-09 | Identification of new targets for immunotherapy of ovarian adenocarcinoma based on the immunopeptidome of tumor cells
BACKGROUND. Ovarian adenocarcinoma is characterized by a high mortality rate due to late diagnosis and the development of resistance to standard chemotherapy. Despite the introduction of targeted therapies, the risk of recurrence remains high, highlighting the need for new therapeutic approaches. In this view, immunotherapy is a promising approach, but requires the identification of specific tumor antigens. AIM. To identify tumor antigens in ovarian adenocarcinoma that are promising for immunotherapy. METHODS. Immunopeptidome from cell lines and postoperative material of patients with ovarian adenocarcinoma were isolated using immunoaffinity chromatography followed by liquid chromatography-mass spectrometry analysis. RESULTS. In this study, we tested an affinity chromatography-based immunopeptidome isolation protocol, comparing various detergents (CHAPS, NP-40, SOD, and Triton X-100) for cell lysis, and observed no statistically significant differences in the number of identified peptides. Using NP-40, 5 peptides belonging to the proteins of cancer/testis antigens (CTA) were identified in the immunopeptidomes of postoperative material from patients with ovarian adenocarcinoma, 3 of which, according to the human protein atlas, are indeed not expressed in normal ovarian tissues. CONCLUSION. Each of the four tested detergents provides identification of unique sets of peptides. Immunopeptidome analysis allows the identification of peptides ofCTA proteins, but a larger sample of postoperative material from patients with ovarian adenocarcinoma and experimental testing of the immunogenicity of the identified peptides are needed for further research.
2026-04-01 | Overexpression of the erythropoietin receptor is associated with upregulation of tubulin beta 6 and paclitaxel resistance in ovarian adenocarcinoma cells.
The emergence of tumor cell resistance is one of the major issues in current oncology practice. It reduces the effectiveness of therapy and worsens cancer patients' prognoses. However, it confirms a wide range of molecular interactions as well as the complexity of the human organism. Our previous research confirmed the functionality of the erythropoietin receptor (EPOR) in ovarian and breast cancer cells, as well as its relationship to these cells' sensitivity to specific therapies. The current study demonstrates that EPOR overexpression in human ovarian adenocarcinoma cells A2780 is directly linked to paclitaxel resistance. Furthermore, EPOR overexpression results in morphological changes that vary according to the pattern of EPOR isotypes expressed. In this regard, the most interesting result appears to be the change in the shape of the T clone, which has a tendency to form spheroidal structures. In addition, functional enrichment analysis demonstrated that EPOR-associated differentially expressed genes are involved in several biological and cell processes. Indeed, a T clone with a single 68 kDa EPOR isotype demonstrates significant resistance to paclitaxel therapy and is associated with the upregulation of tubulin beta 6.
oligonucleotides
2025-11-19 | Long non-coding RNA HCP5 accelerated malignant progression of ovarian cancer by inhibiting ferroptosis through interaction with polypyrimidine tract binding protein 1.
Ovarian cancer (OVCA) is the third most common gynaecological malignancy worldwide. Long non-coding RNA (LncRNA) HCP5 and polypyrimidine tract binding protein 1 (PTBP1) involved in regulating tumors, however, with undefined mechanism in OVCA. After validating lentiviral transfection efficiency, OVCA mouse models were constructed by intraperitoneal injection of ID8-Luc cells for 8 weeks, with sh-lncRNA HCP5, oe-PTBP1, and ferroptosis agonist Erastin treatment. In vivo imaging, tumor metastasis, immunohistochemistry, HE, and TUNEL staining were performed. Human ovarian adenocarcinoma cell SKOV3 cells underwent the same grouping. Interaction between lncRNA HCP5 and PTBP1 was examined using RNA immunoprecipitation and RNA pull-down assay. CCK8, flow cytometry, transmission electron microscopy, biochemical kits, qRT-PCR, and Western blot were performed. In OVCA mice, sh-lncRNA HCP5 inhibited tumor growth and increased tumor tissue pathological damage and apoptosis, with lower PTBP1, Ki67, and B-cell lymphoma-2 (Bcl-2) expression, and higher Bcl-2 associated X and caspase-3 expression. Meanwhile, sh-lncRNA HCP5 induced ferroptosis, with reduced glutathione peroxidase 4, glutathione, and recombinant solute carrier family 7, member 11 expression, and elevated malondialdehyde, lipid peroxides, 4-hydroxynonenoic acid, acyl-CoA synthetase long chain family member 4, and transferrin receptor protein expression. These effects were reversed by oe-PTBP1, and Erastin weakened the pro-tumor role of oe-PTBP1, which were also observed in SKOV3 cells. Additionally, in vitro, lncRNA HCP5 was confirmed to bind to PTBP1, and sh-lncRNA HCP5 reduced cell viability and enhanced reactive oxygen species. LncRNA HCP5 may promote OVCA progression by inhibiting ferroptosis through interaction with PTBP1, providing new targets in OVCA treatment.
2025-10-14 | Fe 3 O 4 @Au loaded with PNPO-siRNA for the diagnosis and treatment of ovarian cancer
Aim To design and fabricate composite magnetic nanoparticles (MNPs), Fe3O4@Au(Cy5.5)-DOPE/PNPO-siRNA, for the diagnosis and treatment of ovarian cancer (adenocarcinoma cells).Materials and methods Fe3O4@Au(Cy5.5)-DOPE/PNPO-siRNA nanoparticles were synthesized using seed growth and chemical reduction methods. The fabricated Fe3O4@Au nanoparticles were systematically characterized and evaluated. For in vitro studies, the anti-tumor effects were assessed in naturally resistant SKOV3 ovarian adenocarcinoma cells. Cellular uptake, gene-silencing efficiency, and cytotoxicity assays were conducted to determine their therapeutic potential. For in vivo studies, a xenograft mouse model harboring SKOV3 tumors was established to evaluate magnetic resonance imaging (MRI) contrast enhancement and biosafety of nanoparticles. MRI was performed using T2-weighted imaging (T2WI) to monitor tumor accumulation and signal changes. The biosafety was further examined through histopathological analysis of major organs.Results We successfully designed and fabricated Fe3O4@Au composite magnetic nanoparticles (MNPs) encapsulated with surface lipids, which exhibited excellent biocompatibility and safety. These Fe3O4@Au composite MNPs effectively delivered PNPO-siRNA into SKOV3 cells, enabling both ovarian cancer treatment and MRI. In vivo MRI of SKOV3 tumor-bearing mice showed effective tumor accumulation of nanoparticles. T2WI revealed a peak signal reduction of approximately 17% at 3h post-injection (ANOVA, compared to the pre-injection group, ***p < 0.001), followed by gradual recovery over time. These findings indicate that Fe3O4@Au MNP can serve as effective negative MRI contrast agent to enhance ovarian cancer detection. For therapeutic evaluation, Fe3O4@Au(Cy5.5)-DOPE/PNPO-siRNA nanoparticles significantly inhibited SKOV3 cell proliferation in vitro. Furthermore, biosafety assessments demonstrated no significant toxicity in major organs, supporting their potential for as a safe and effective platform for the treatment of ovarian cancer.Conclusion Fe3O4@Au(Cy5.5)-DOPE/PNPO-siRNA composite magnetic MNPs demonstrate significant potential as dual-function agents, serving both as MRI tracers and as molecular therapeutic platforms for ovarian cancer in vivo.
2024-06-06 | The consequences of manipulating relaxin family peptide receptor 1 (RXFP1) level in ovarian cancer cells.
Deregulation of the relaxin family peptide system (RFPS) appears to increase the risk of range of cancers, including epithelial ovarian cancers (EOC). The present study examines the effect of relaxin family peptide receptor 1 (RXFP1) level on the biological properties of human epithelial ovarian adenocarcinoma cells (OVCAR4 and SKOV3). RXFP1 was downregulated (RXFP1↓) in the cells using the RXFP1 sgRNA CRISPR All-in-One Lentivirus set (pLenti-U6-sgRNA-SFFV-Cas9-2A-Puro), and upregulated (RXFP1↑) using the RXFP1 CRISPRa sgRNA Lentivector (pLenti-U6-sgRNA-PGK-Neo) kit, which activates the RXFP1 gene when paired with dCas9-SAM. The changes taking place during adhesion to extracellular matrix (ECM) proteins were assessed in multi-well plates coated with collagen, fibronectin, laminin and gelatin. Cellular viability was monitored based on mitochondrial metabolic activity (MTT Assay, Alamar Blue Assay) and adenosine triphosphate production (ATP Assay). The rate of cell proliferation was determined based on the percentage of Ki67 immunoreactive cells and the numbers of cells in particular cell-cycle phases. The mesenchymal-like (Boyden Chamber Assay) and amoeboid-like movements (Wound Healing Assay) of ovarian cancer cells were also analyzed after transfection. RXFP1 downregulation decreased the adhesion properties of ovarian cancer cells and increased the tendency for apoptosis under stressful conditions. In contrast, RXFP1 upregulation had pro-proliferative, pro-survival and promigratory effects. Our findings confirm that the relaxin-2/RXFP1 signaling pathway plays a role in the promotion of growth and progression of ovarian cancer.
2024-03-19 | High expression levels of centromere protein O participates in cell activity of human ovarian cancer
Abstract Ovarian cancer is a common malignant tumor in women, with a high mortality rate ranking first among gynecological tumors. Currently, there is insufficient understanding of the causes, pathogenesis, recurrence and metastasis of ovarian cancer, and early diagnosis and treatment still face great challenges. The sensitivity and specificity of existing ovarian cancer screening methods are still unsatisfactory. Centromere protein O (CENP-O) is a recently discovered structural centromere protein that is involved in cell death and is essential for spindle assembly, chromosome separation, and checkpoint signaling during mitosis. The abnormal high expression of CENP-O was detected in various tumors such as bladder cancer and gastric cancer, and it participates in the regulation of tumor cell proliferation. In this study, we detect the expression abundance of CENP-O mRNA in different ovarian cancer cells ( ES-2, A2780, Caov-3, OVCAR-3 and SK-OV-3). The biological function changes of cell proliferation and apoptosis were detected and the role of CENP-O in ovarian cancer cell proliferation and apoptosis was explored by knocking down the expression of CENP-O gene. The results showed that CENP-O gene was significantly expressed in 5 types of ovarian cancer cell lines. After knocking down the CENP-O gene, the proliferation and cloning ability of ovarian cancer cells decreased, and the apoptosis increased. This study indicates that CENP-O has the potential to be a molecular therapeutic target, and downregulating the expression of CENP-O gene can break the unlimited proliferation ability of cancer cells and promote their apoptosis, providing a foundation and new ideas for subsequent molecular mechanism research and targeted therapy.
2023-07-20 | ZFP57 promotes ovarian cancer progression by transcriptionally regulating BRCA1 and managing G1 checkpoint
Ovarian cancer (OC) which is one of the frequently-occurring gynecologic malignant tumors, endangers the health of women. The zinc finger protein 57 (ZFP57) plays crucial functions during the progression of cancer and is reported as a prognostic and therapeutic candidate in a variety of cancer. However, the biological function as well as the underlying mechanism of ZFP57 during OC progression remains unknown. Here, ZFP57 expression was found prominently increased in OC tissues and correlated with the prognosis of OC patients. Knock down of ZFP57 in OC cells inhibited the cell proliferation and migration, and also arrested the cells at G1 phase as well as accelerated the apoptosis. Additionally, ZFP57 transcriptionally regulated BRCA1 expression in OC, indicating that ZFP57 may affect BRCA1 mediated G1 checkpoint to regulate the cell cycle of OC cells and further influence the progression of OC. Taken together, our present study discovered a novel function of ZFP57 in OC, suggesting that ZFP57 could be potentially treated as a prognostic biomarker and therapeutic target for OC patients.
other
2026-04-21 | Intraperitoneal administration of NK-92 improves survival in xenografts of early and established ovarian cancer models.
Ovarian cancer (OC) is a leading cause of gynecological cancer-related mortality. Management remains challenging as the disease frequently presents with intra-abdominal metastases at diagnosis, standard therapies can be associated with severe complications and disease recurrence is common. While cellular immunotherapy is increasingly investigated as a promising approach, the most effective routes of administration need to be established. We have investigated NK cell therapeutics as a less toxic option and examined the permanent NK cell line, NK-92, as a suitable model. Here, we report two xenograft mouse models with the ovarian adenocarcinoma cell line, SKOV-3, representing early-stage OC and late-stage OC with ascites to comprehensively evaluate the anti-cancer efficacy of different routes of NK-92 administration. Bioluminescence imaging, cell tracking with the IVIS system and animal survival were used to evaluate outcomes. The cells were administered via intraperitoneal (IP), intravenous (IV), or a combination of IP and IV routes. We showed that NK-92 significantly increased animal survival when delivered IP (p = 0.009 and p = 0.018) or combined IP and IV (p = 0.05 and p = 0.017) in early and established OC xenografts, respectively, whereas intravenous delivery at similar doses had no effect on survival (p = 0.665 and p = 0.052) compared with untreated controls. These findings, and our novel models, have potential implications for enhancing the clinical benefit of NK therapy in patients with advanced OC.
2025-03-05 | CRISPR-Cas9 knockout of DGKα/ζ improves the anti-tumor activities of TAG-72 CAR-T cells in ovarian cancer
High recurrence and chemoresistance in solid tumors, like ovarian cancer, stress the need for new therapies. Chimeric antigen receptor (CAR)-T cells show promise but face challenges due to tumor heterogeneity and immune suppression in the tumor microenvironment (TME). Thus, novel approaches are needed to further enhance the efficacy of CAR-T cell therapies. In T cell therapies, inhibiting checkpoint molecules is crucial for overcoming exhaustion and boosting anti-tumor activity. Additionally, prioritizing safety by engineering cells to target markers absent on normal healthy cells reduces off-target risks. We targeted tumor-associated glycoprotein 72 (TAG-72), an oncofetal antigen highly expressed in adenocarcinomas like ovarian cancer, by engineering TAG-72 CAR-T cells and used CRISPR-Cas9 to knock out the T cell-inhibitory enzymes diacylglycerol kinase (DGK) α and ζ. DGKα/ζ knockout (KO) did not impact CAR-T cell viability or phenotype. These cells selectively killed TAG-72-expressing cancer cells in vitro and ablated established tumors in vivo for up to 100 days, whereas non-deleted control TAG-72 CAR-T cells showed tumor relapse around 40 days. These findings highlight the potential of CRISPR-induced DGKα/ζ KO to enhance CAR-T cell efficacy against solid tumors such as ovarian cancer, offering a promising avenue for improved cancer therapies.
2024-06-01 | Phase I/II study of TROP2 CAR engineered IL15-transduced cord blood-derived NK cells delivered intraperitoneally for the management of platinum resistant ovarian cancer, mesonephric-like adenocarcinoma, and pancreatic cancer.
TPS5626 Background: Novel treatments are needed for patients with ovarian, pancreatic, and mesonephric-like adenocarcinoma (MLA) that has recurred or progressed after initial treatment, as current standard of care therapies in these settings result in low response rates. Chimeric antigen receptor-transduced natural killer (CAR-NK) cells have emerged as a therapeutic alternative to CAR-T cells, with decreased toxicity and enhanced feasibility as an “off-the-shelf” therapy. TROP2, or trophoblast cell-surface antigen 2, is a transmembrane calcium-signal transducer that is overexpressed in many cancer types and associated with poor clinical outcomes. Recent studies have demonstrated TROP2 as a promising target for adoptive cell therapy in breast and gastric cancers. An intraperitoneal route of adoptive cell therapy delivery may provide superior disease control and decreased toxicity in these target cancers with predisposition for intra-abdominal/peritoneal involvement. Pre-clinical studies have established the efficacy and safety of TROP2 CAR NK cells in ovarian and pancreatic cancers. Methods: This is a phase I/II study of the intraperitoneal delivery of TROP2-CAR/IL-15 transduced cord blood (CB)-NK cells for recurrent/progressive ovarian cancer, pancreatic cancer, and MLA (NCT05922930). Subjects must have disease present in the peritoneal cavity or retroperitoneal lymph nodes and tumors must demonstrate at least 1+ TROP2 expression by immunohistochemistry. The primary endpoints are toxicity rates and defining the recommended phase II dose (RP2D). Key secondary endpoints include treatment efficacy, circulating tumor DNA levels, serial characterization of the immune microenvironment, and patient-reported outcomes. There are four possible dose levels ranging from 8.0x10 6 to 4.0x10 9 cells. We will enroll patients from the three disease cohorts using the Bayesian optimal interval (BOIN) design to find the maximum tolerated dose and RP2D, with a maximum sample size of 21. Once the R2PD is chosen, we will enroll up to 10 patients within each disease cohort to further evaluate safety and efficacy. Subjects enrolled will be admitted to the hospital, receive lymphodepleting chemotherapy (fludarabine 30 mg/m 2 and cyclophosphamide 300mg/m 2 ) on days -5 to -3, and will receive a single dose of cryopreserved and thawed intraperitoneal TROP2-CAR/IL15-transduced CB-NK cells on day 0. The dose-limiting toxicity window will be from day 0 until day 28. Severity of adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5. The first patient on this trial was treated in January 2024. Clinical trial information: NCT0592293 .
2024-04-30 | Comprehensive Bioinformatic Investigation of TP53 Dysregulation in Diverse Cancer Landscapes
P53 overexpression plays a critical role in cancer pathogenesis by disrupting the intricate regulation of cellular proliferation. Despite its firmly established function as a tumor suppressor, elevated p53 levels can paradoxically contribute to tumorigenesis, influenced by factors such as exposure to carcinogens, genetic mutations, and viral infections. This phenomenon is observed across a spectrum of cancer types, including bladder (BLCA), ovarian (OV), cervical (CESC), cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), diffuse large B-cell lymphoma (DLBC), esophageal carcinoma (ESCA), head and neck squamous cell carcinoma (HNSC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and uterine corpus endometrial carcinoma (UCEC). This broad spectrum of cancers is often associated with increased aggressiveness and recurrence risk. Effective therapeutic strategies targeting tumors with p53 overexpression require a comprehensive approach, integrating targeted interventions aimed at the p53 gene with conventional modalities such as chemotherapy, radiation therapy, and targeted drugs. In this extensive study, we present a detailed analysis shedding light on the multifaceted role of TP53 across various cancers, with a specific emphasis on its impact on disease-free survival (DFS). Leveraging data from the TCGA database and the GTEx dataset, along with GEPIA, UALCAN, and STRING, we identify TP53 overexpression as a significant prognostic indicator, notably pronounced in prostate adenocarcinoma (PRAD). Supported by compelling statistical significance (
2024-03-17 | CD40 stimulation via CD40 ligand enhances adenovirus‐mediated tumour immunogenicity including ‘find‐me’, ‘eat‐me’, and ‘kill‐me’ signalling
Abstract Immunostimulatory gene therapy using oncolytic viruses is currently evaluated as a promising therapy for cancer aiming to induce anti‐tumour immunity. Here, we investigate the capacity of oncolytic adenoviruses (LOAd) and their transgenes to induce immunogenicity in the infected tumour cells. Oncolysis and death‐related markers were assessed after infection of eight human solid cancer cell lines with different LOAd viruses expressing a trimerized, membrane‐bound (TMZ)‐CD40L, TMZ‐CD40L and 41BBL, or no transgenes. The viruses induced transgene expression post infection before they were killed by oncolysis. Death receptors TRAIL‐R1, TRAIL‐R2 and Fas as well as immunogenic cell death marker calreticulin were upregulated in cell lines post infection. Similarly, caspase 3/7 activity was increased in most cell lines. Interestingly, in CD40 + cell lines there was a significant effect of the TMZ‐CD40L‐encoding viruses indicating activation of the CD40‐mediated apoptosis pathway. Further, these cell lines showed a significant increase of calreticulin, and TRAIL receptor 1 and 2 post infection. However, LOAd viruses induced PD‐L1 upregulation which may hamper anti‐tumour immune responses. In conclusion, LOAd infection increased the immunogenicity of infected tumour cells and this was potentiated by CD40 stimulation. Due to the simultaneous PD‐L1 increase, LOAd viruses may benefit from combination with antibodies blocking PD1/PD‐L1.
small molecules
2026-08-17 | Design, Synthesis, and Evaluation of Alkoxyamine Anticancer Prodrugs Bearing Galactoside as an Enzyme-Activated Trigger.
Enzyme-induced cytotoxicity can be considered the main challenge in modern cancer therapy that provides unique opportunities for targeted apoptosis. To address this challenge, we implemented enzyme-triggered activation of alkoxyamine-galactose conjugates with the formation of active carbon-centered radical species for the apoptosis of cancer cells. The comparative analysis of two alkoxyamine derivatives, bearing stable and self-immolative linkers between the radical precursor and galactose moiety, revealed the crucial role of molecular structure in anticancer activity. The study of cytotoxicity and induced oxidative stress of free amine and two galactosides revealed the enzyme-dependent nature of the activity of alkoxyamines having a self-immolative linker against distinct cancer cell lines such as PC-3 (prostate adenocarcinoma), SKOV-3 (ovarian adenocarcinoma), MCF-7 (breast adenocarcinoma), A-431 (epidermoid carcinoma), and Jurkat cells (human T-lymphoblastic leukemia). The collected data prove the applicability of enzyme-triggered glycosylated alkoxyamines as a new family of targeted prodrugs against cancer.
2026-07-16 | Anticancer potential of β-isopropylfuran-1,2-naphthoquinone in different types of tumor cell lines.
Cancer is a multifactorial disease characterized by uncontrolled cell growth and remains a major global health challenge. Given the limitations of conventional therapies, naturally derived compounds such as naphthoquinones have attracted interest for their antitumor potential. This study evaluated the in vitro effects of β-isopropylfuran-1,2-naphthoquinone (NAF-Q69), a synthetic isolapachol derivative, on different cell lines (MRC-5 - human lung fibroblasts; HEPG2 - hepatocellular carcinoma; HeLa - cervical cancer; TOV - ovarian adenocarcinoma; MDA-MB - breast adenocarcinoma; and J82 - urothelial carcinoma) to assess its cytotoxic activity and cellular characteristics (clonogenic survival, migration, morphology, cell cycle, and reactive oxygen species \[ROS] production). NAF-Q69 showed significant dose-dependent cytotoxicity in all tumor lines, with IC50 values ranging from 10.29 µM (MDA-MB) to 18.65 µM (HEPG2). It decreased viability, inhibited colony formation, and impaired migration, particularly in TOV, HeLa, and HEPG2 cells. Morphological alterations were evident. The compound induced cell death, with increased sub-G1 populations, and promoted G2/M arrest. Moreover, NAF-Q69 markedly elevated ROS levels, implicating oxidative stress as a central mechanism. In conclusion, NAF-Q69 exhibits promising antitumor activity by inhibiting proliferation and migration, inducing cell death, and enhancing oxidative stress, supporting the potential of naphthoquinones in cancer therapy.
2026-06-06 | Overexpression of scavenger receptor class B member 2 leads to different response of ovarian adenocarcinoma cells to chemotherapy.
Scavenger Receptor Class B Member 2 (SCARB2) is an integral lysosomal membrane protein essential for lysosomal integrity and autophagy regulation. The aim of this study was to investigate the functional impact of SCARB2 overexpression on chemotherapy response, reactive oxygen species (ROS) production and proteomic composition of human ovarian adenocarcinoma cells A2780. To induce SCARB2 overexpression, A2780 cells were transfected using a PiggyBac vector system. Two clones with the highest SCARB2 expression (L and V) were selected for further analyses. Differences in chemosensitivity were assessed using the MTS assay. Proteomic analysis was used to identify differentially expressed proteins and enriched pathways. We also performed flow cytometry to investigate changes in ROS production and lysosomal activity. Lysosomal distribution was assessed using LAMP1 immunofluorescence staining followed by confocal microscopy, and total cholesterol levels were determined using an enzymatic colorimetric assay. Both clones showed increased sensitivity to cisplatin compared to the control group. In contrast, clone V showed resistance to doxorubicin and no significant differences were observed for gemcitabine, except for a transient sensitizing effect when low concentrations used. Elevated ROS levels were detected in untreated clones, and after doxorubicin exposition. Proteomic analysis showed significant changes in lysosome-associated proteins, with consistent enrichment of the lysosomal pathway across all experimental comparisons. Immunofluorescence analysis of LAMP1 and LysoTracker staining demonstrated altered lysosomal distribution and activity in SCARB2-overexpressing clones. In addition, both SCARB2-overexpressing clones exhibited significantly reduced total cholesterol levels compared with control cells. This study broadens our understanding of SCARB2 in ovarian cancer. SCARB2 overexpression induces extensive lysosomal reprogramming in A2780 ovarian cancer cells and modulates chemotherapy response.
2026-05-01 | Punicalagin Inhibits the Growth and Proliferation of Ovarian Epithelial Adenocarcinoma Cells Via Apoptosis and Autophagic Cell Death
Ovarian cancer remains a leading cause of gynecologic cancer-related mortality and is frequently associated with therapeutic resistance. Punicalagin (PCG), a pomegranate-derived polyphenol, has demonstrated anticancer activity in multiple tumor models, however, its effects in ovarian cancer require further clarification. This study evaluated the anti-proliferative and anti-migratory effects of PCG in two biologically distinct ovarian cancer cell lines, OVCAR-3 and SKOV-3. PCG treatment (6.25-200 µM) significantly reduced cell viability and colony formation in a dose- and time-dependent manner. Migration-associated behaviors were suppressed in wound-healing and transwell assays, accompanied by modulation of epithelial-mesenchymal transition markers, including increased E-cadherin and decreased N-cadherin expression. PCG increased reactive oxygen species (ROS) levels and reduced mitochondrial membrane potential in both cell lines. Annexin V/propidium iodide analysis demonstrated increased apoptotic cell populations, with elevated BAX expression. Autophagy-related changes, including LC3-I to LC3-II conversion and acridine orange-positive vesicles, were observed in OVCAR-3 cells but not in SKOV-3 cells. Collectively, these findings indicate that PCG exerts anti-proliferative and pro-apoptotic effects in ovarian cancer cells and is associated with oxidative stress and mitochondrial dysfunction. Further studies are required to define the mechanistic contribution of ROS and autophagy and to evaluate translational relevance in vivo.
2026-04-13 | Organoids serve as viable in vitro model for functional precision medicine for mesonephric-like adenocarcinoma of the ovary
Abstract Background Mesonephric-like adenocarcinoma has been recently classified as a rare type of ovarian carcinoma. Description of these tumours have been rare and mostly covered in case reports. In some cases, molecular characterization by sequencing has been employed for guided therapy recommendations, however, functional chemosensitivity testing of targetable pathways using advanced in vitro cellular models such as organoids has not been reported so far. Here, we report on a case of ovarian cancer that was later identified as mesonephric-like adenocarcinoma at an advanced stage. Methods The tumour was characterized by molecular techniques including immunohistochemistry and whole-exome sequencing. At the same time, ovarian cancer organoids were established by adapting existing protocols for high-grade serous ovarian carcinoma. The organoids were subsequently used for functional in vitro chemosensitivity testing by treatment with standard-of-care chemotherapeutics cisplatin, paclitaxel, and the Poly (ADP-Ribose) Polymerase 1-inhibitor olaparib. Based on molecular characteristics, we also applied the inhibitor binimetinib, to target Mitogen-Activated Protein Kinase downstream of the KRAS Proto-Oncogene. Additionally, chemotoxicity testing with healthy fallopian tube organoids and high-grade ovarian cancer organoids was applied to determine the therapeutic window. Results Immunohistochemical analysis showed characteristic PAX8 + , GATA3 + , TFF1 + , ER - , PR - , WT1 - staining while the sequencing revealed mutations in 31 genes of which KRAS G12V and DYNC1H1 G4072S were annotated as (likely) pathogenic. The tumour was mismatch-repair proficient. Tumour-derived organoids proved to be highly resistant to standard-of-care chemotherapeutics cisplatin, paclitaxel, and olaparib, but sensitive to inhibition by binimetinib, which aligned well with the molecular characteristics. Direct comparison to healthy fallopian tube organoids and high-grade ovarian cancer organoids confirmed low cytotoxic potential underlining a feasible therapeutic window for binimetinib. Conclusions For the first time, we show that existing protocols for high-grade serous ovarian carcinoma can be used for the generation of organoids derived from mesonephric-like adenocarcinoma. These organoids could be used as an essential tool for functional precision medicine purposes. This functional data could be applied as an additional layer for molecular tumour boards diagnostics by supporting molecular datasets and even identify targetable pathways beyond genetic variations, thus offering novel therapeutic options particularly for rare and aggressive tumours.
proteins
2026-01-26 | Overexpression of biliverdin reductase A leads to ROS-independent sensitization of ovarian adenocarcinoma cells to gemcitabine.
Biliverdin reductase A (BLVRA) is a key enzyme in bilirubin metabolism, where it reduces biliverdin to bilirubin. Bilirubin is a potent antioxidant that protects cells from oxidative stress. Therefore, reduced or deregulated BLVRA activity may contribute to increased oxidative DNA damage, which is one of the factors leading to the neoplastic transformation of cells. Human ovarian adenocarcinoma A2780 cells were transfected with a PiggyBac vector to achieve BLVRA overexpression. A2780 clones showing the most significant BLVRA gene overexpression were analyzed by proteomics and flow cytometry to assess rective oxygen species (ROS) production. Our results indicate that BLVRA overexpression increases the sensitivity of A2780 cells to doxorubicin and gemcitabine, with the most pronounced effect observed in the J clone. In this clone, the highest level of BLVRA overexpression correlated with significant alterations in the p53 signaling pathway. Upregulation of key effectors such as Bax and CDKN2A indicates a potential role for BLVRA in promoting pro-apoptotic responses. Moreover, BLVRA overexpression increased the sensitivity of A2780 cells to gemcitabine independently of ROS. This study broadens our understanding of BLVRA in ovarian cancer. In cells with intact p53 signaling, BLVRA overexpression can paradoxically enhance cytotoxic response to certain drugs, particularly gemcitabine.
2025-07-31 | Ultrabright NIR-II Nanoprobes for Ex Vivo Bioimaging: Protein Nanoengineering Meets Molecular Engineering
ABSTRACT Near-infrared (NIR) fluorescence imaging is a powerful, non-invasive tool for cancer diagnosis, enabling real-time, high-resolution visualization of biological systems. While most probes target the first NIR window (NIR-I, 750-950 nm), recent advances focus on the second window (NIR-II, 1000-1700 nm), which offers deeper tissue penetration and reduced interferences from scattering and autofluorescence. However, many current NIR-II nanoprobes show suboptimal brightness and limited validations in more human-centric models. Here, we present an orthogonal strategy combining molecular engineering, by modulating the amount and position of thiophene moieties in semiconducting polymers (SPs), with protein nanoengineering to develop ultrabright NIR-II imaging probes optimized for ex vivo bioimaging in large animal models. The molecular tuning amplifies the NIR-II fluorescence brightness while screening endogenous proteins as encapsulating matrices to improve colloidal stability and enable active targeting. Molecular docking identified bovine serum albumin as the effective candidate, and the resulting protein-complexed nanoprobes were characterized for size, colloidal stability under physiological conditions, and optical performances. Imaging performances were evaluated using tumor-mimicking phantoms in porcine lungs, simulating cancer surgery, and injected at clinically relevant concentrations into ovine brains and porcine ovaries for microvascular visualization and tissue discrimination, respectively. In all scenarios, our protein-complexed nanoprobes outperformed the FDA-approved clinical dye indocyanine green in signal-to-background ratios. Initial in vitro assays confirmed their hemocompatibility, biocompatibility, and cellular uptake in ovarian adenocarcinoma cells. This integrated approach offers a promising platform for developing next-generation ultrabright NIR-II nanoprobes with improved brightness and stability, advancing the potential for image-guided surgery and future clinical translation. Abstract Figure
2024-08-22 | The first-in-class pro-apoptotic peptide PEP-010 is effective in monotherapy and in combination with paclitaxel on resistant ovarian adenocarcinoma cell models.
Ovarian adenocarcinoma is the gynecological malignancy with the worst prognosis and the highest mortality rate. In the first stages of treatment, chemotherapy results effective, but its prolonged use and high doses lead to the appearance of resistance to treatments and relapse in most patients, representing a major challenge for clinicians. We developed PEP-010, a cell penetrating proapoptotic peptide disrupting the protein-protein interaction between caspase-9 and protein phosphatase 2A, thereby leading to the recovery of their activity in the apoptotic pathway. MTT assay or Annexin-V/Propidium Iodide staining and flow cytometry analysis were used to assess sensitivity to chemotherapies and apoptosis after treatment with PEP-010 in monotherapy or in combination with paclitaxel in ovarian carcinoma cell lines. DNA damage was assessed by immunofluorescence using γH2AX marker. We show here that PEP-010 effectively induces cell death in monotherapy on in up to 55% of cells from ovarian adenocarcinoma cell models resistant to different chemotherapies. Moreover, when used in combination with paclitaxel, one of the therapeutic options for recurrent ovarian carcinoma, PEP-010 showed a beneficial effect leading to the reduction of the IC50 of paclitaxel of 2.2 times and to apoptosis in 87% of cells. The described results suggest the potential therapeutic interest for PEP-010 and lead to the choice of ovarian adenocarcinoma as one of the major indications of the ongoing clinical trial.
2024-06-01 | A phase I open-label study of a novel IL-2Rβ/γ cytokine agonist, LTC004, in patients with advanced or metastatic solid tumors.
2652 Background: LTC004, a novel IL-2Rβ/γ cytokine agonist, designed to minimize toxicity with improved potency. It has selective affinity for the receptor IL-2Rβγ subunits, preferentially stimulates CD8 + effector T cells and natural killer cells which are associated with tumor killing, while minimizing the activation of immunosuppressive regulatory T cells. LTC004 has shown significant in vitro and in vivo anti-tumor activity in multiple cell lines and murine models respectively. Methods: This is a first-in-human, multicenter, open-label, dose-escalation and dose-expansion phase I study of LTC004 in advanced solid tumors. Dose escalation part assessed safety and tolerability of intravenous LTC004 with doses ranging from 3.0 to 360 µg/kg. The dose escalation schedule utilized an accelerated titration and Bayesian Optimal Interval (BOIN) design. Eligible pts with advanced solid tumor were required to have received prior standard therapy. LTC004 is administrated intravenously once every 3 weeks. Results: The study completed dose-escalation part (3.0 to 360 µg/kg) as of cutoff date (Jan 10, 2024). 17 pts of multiple tumor types (including non-small cell lung, cervical, colorectal, sarcoma, melanoma, parotid adenocarcinoma, thymic adenocarcinoma, gastric and ovarian cancers) were enrolled and received ≥1 dose of LTC004. At baseline, 12 pts (70.6%) had received ≥2 prior lines therapy, 11 pts (64.7%) had received prior targeted therapy, 10 pts (58.8%) had received prior immune checkpoint inhibitor (ICI) therapy. LTC004 generally well tolerated and no dose-limiting toxicities (DLTs) up to and including 360 µg/kg was observed. The most common TEAEs overall in ≥30% of pts were fever, white blood cell decreased, anemia, AST/ALT increased, neutrophil count decreased, GGT increased, nausea and hypotension. Most of the reported AEs were G1 and G2, all drug related events reversible and responsive to supportive care therapy. Fever can be resolved with standard anti-pyretic treatment or steroids, transient hypotension can be preventable with prophylactic fluid infusion. Of 17 pts enrolled evaluable for efficacy per RECIST v1.1, the ORR were 5.9% (1/17), DCR were 58.8% (10/17). A confirmed PR was achieved in a pMMR/MSS CRC patient with prior therapies including fluoropyrimidines, irinotecan, oxaliplatin, targeted therapy and TKI. The starting dose was 45µg/kg, titration to 90µg/kg after 4 consecutive doses at 45µg/kg Q3W. As of cutoff date, the patient sustained PR for 4.8 months with follow-up ongoing. Conclusions: LTC004 demonstrated encouraging anti-tumor efficacy including cold tumor, and well tolerated in patients with advanced or metastatic solid tumors. The further dose expansion in selected tumor types is ongoing, and evaluations in combination with other agents are being planned. Clinical trial information: NCT05666635 .
2024-02-01 | RGD peptide in cancer targeting: Benefits, challenges, solutions, and possible integrin-RGD interactions.
Abstract RGD peptide can be found in cell adhesion and signaling proteins, such as fibronectin, vitronectin, and fibrinogen. RGD peptides' principal function is to facilitate cell adhesion by interacting with integrin receptors on the cell surface. They have been intensively researched for use in biotechnology and medicine, including incorporation into biomaterials, conjugation to medicinal molecules or nanoparticles, and labeling with imaging agents. RGD peptides can be utilized to specifically target cancer cells and the tumor vasculature by engaging with these integrins, improving drug delivery efficiency and minimizing adverse effects on healthy tissues. RGD‐functionalized drug carriers are a viable option for cancer therapy as this focused approach has demonstrated promise in the future. Writing a review on the RGD peptide can significantly influence how drugs are developed in the future by improving our understanding of the peptide, finding knowledge gaps, fostering innovation, and making drug design easier.
antibodies
2026-07-21 | Abstract A005: VBC106: A First-in-class FOLR1/MSLN Targeted Tri-specific Antibody Drug Conjugate (ADC) in Ovarian Cancer, Endometrial Cancer, Lung Adenocarcinoma and Beyond
Abstract FOLR1 and MSLN are GPI-anchored proteins involved in cancer pathogenesis. The therapeutic potential of targeting FOLR1 is demonstrated by the approval of Elahere (mirvetuximab soravtansine-gynx; IMGN853). However, Elahere selects patients with FOLR1 high expression (TPS≥75), and poses safety concern of severe ocular toxicities. Recently, RC88 showed preliminary efficacy in patients with IHC 2+ or higher MSLN expression, highlighting MSLN as a potential therapeutic target. Despite this, unmet needs remain for patients with low FOLR1 or MSLN expression. Notably, FOLR1 and MSLN are highly co-expressed in solid tumors like ovarian cancer, endometrial cancer, lung adenocarcinoma and so on, but limited in normal tissues, offering an opportunity for tumor-specific targeting and supporting bispecific designs. VBC106 is a tri-specific antibody-drug conjugate (ADC) targeting both FOLR1 and MSLN. It delivers a TOPOi payload with a strong bystander effect, maximizing efficacy while minimizing safety concerns. VBC106 distinguishes itself from other drugs targeting FOLR1 and/or MSLN with the following features: Optimized Structure: VBC106 has a high-avidity bi-paratopic FOLR1 arm and a high-affinity MSLN arm, the structure was optimized to enhance synergistic binding and achieve maximum internalization. High in-vitro Potency: VBC106 demonstrates stronger cytotoxicity and a more potent bystander effect than Elahere analogues and PRO1184. Superior in-vivo Efficacy in CDX: In over 10 CDX models of various cancer types, VBC106 showed superior efficacy compared to Elahere analogues and PRO1184. And it is effective in FOLR1 low-expression models where others are not. High Response Rate in PDX: VBC106 shows a high response rate in PDX models across multiple cancer types. Good Pharmacokinetics: In NHP, VBC106 has a half-life of about 4 days. Large Therapeutic Window: GLP toxicity studies in cynomolgus monkeys indicate good tolerability at repeated doses. The HNSTD is 40 mg/kg. In summary, VBC106, with its unique tri-specific design and differentiated features, has superior efficacy and high safety, making it a promising first-in-class ADC candidate for clinical development, with a U.S. IND submission planned for Q2 2026. Citation Format: Man Xu, Xuekun Zhang, Wei Wang, Kevin Yin, Yajun Huang, Yanling Gong, Yingchun Wang, Jing Li. VBC106: A First-in-class FOLR1/MSLN Targeted Tri-specific Antibody Drug Conjugate (ADC) in Ovarian Cancer, Endometrial Cancer, Lung Adenocarcinoma and Beyond [abstract]. In: Proceedings of AACR Drug Discovery and Development (AACR D3) Conference; 2026 Jul 21-24; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(14_Suppl):Abstract nr A005.
2026-07-21 | Abstract PR008: VBC106: A First-in-class FOLR1/MSLN Targeted Tri-specific Antibody Drug Conjugate (ADC) in Ovarian Cancer, Endometrial Cancer, Lung Adenocarcinoma and Beyond
Abstract FOLR1 and MSLN are GPI-anchored proteins involved in cancer pathogenesis. The therapeutic potential of targeting FOLR1 is demonstrated by the approval of Elahere (mirvetuximab soravtansine-gynx; IMGN853). However, Elahere selects patients with FOLR1 high expression (TPS≥75), and poses safety concern of severe ocular toxicities. Recently, RC88 showed preliminary efficacy in patients with IHC 2+ or higher MSLN expression, highlighting MSLN as a potential therapeutic target. Despite this, unmet needs remain for patients with low FOLR1 or MSLN expression. Notably, FOLR1 and MSLN are highly co-expressed in solid tumors like ovarian cancer, endometrial cancer, lung adenocarcinoma and so on, but limited in normal tissues, offering an opportunity for tumor-specific targeting and supporting bispecific designs. VBC106 is a tri-specific antibody-drug conjugate (ADC) targeting both FOLR1 and MSLN. It delivers a TOPOi payload with a strong bystander effect, maximizing efficacy while minimizing safety concerns. VBC106 distinguishes itself from other drugs targeting FOLR1 and/or MSLN with the following features: Optimized Structure: VBC106 has a high-avidity bi-paratopic FOLR1 arm and a high-affinity MSLN arm, the structure was optimized to enhance synergistic binding and achieve maximum internalization. High in-vitro Potency: VBC106 demonstrates stronger cytotoxicity and a more potent bystander effect than Elahere analogues and PRO1184. Superior in-vivo Efficacy in CDX: In over 10 CDX models of various cancer types, VBC106 showed superior efficacy compared to Elahere analogues and PRO1184. And it is effective in FOLR1 low-expression models where others are not. High Response Rate in PDX: VBC106 shows a high response rate in PDX models across multiple cancer types. Good Pharmacokinetics: In NHP, VBC106 has a half-life of about 4 days. Large Therapeutic Window: GLP toxicity studies in cynomolgus monkeys indicate good tolerability at repeated doses. The HNSTD is 40 mg/kg. In summary, VBC106, with its unique tri-specific design and differentiated features, has superior efficacy and high safety, making it a promising first-in-class ADC candidate for clinical development, with a U.S. IND submission planned for Q2 2026. Citation Format: Man Xu, Xuekun Zhang, Wei Wang, Kevin Yin, Yajun Huang, Yanling Gong, Yingchun Wang, Jing Li. VBC106: A First-in-class FOLR1/MSLN Targeted Tri-specific Antibody Drug Conjugate (ADC) in Ovarian Cancer, Endometrial Cancer, Lung Adenocarcinoma and Beyond [abstract]. In: Proceedings of AACR Drug Discovery and Development (AACR D3) Conference; 2026 Jul 21-24; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(14_Suppl):Abstract nr PR008.
2026-07-01 | Complete Remission of Erythrodermic Psoriasis After Bevacizumab Administration for Ovarian Serous Adenocarcinoma: A Case Report
ABSTRACT Patients who have both erythrodermic psoriasis and advanced ovarian cancer are uncommon in clinical practice. This case study presents the case of a patient diagnosed with erythrodermic psoriasis for a duration exceeding 4 years. The patient was administered ixekizumab and adalimumab, but no remission was observed during the illness. The patient was diagnosed with metastatic ovarian serous adenocarcinoma involving multiple lymph nodes and liver in 2022. During her bevacizumab treatment, she experienced a complete remission of psoriasis without any other management for psoriasis.
2026-06-09 | Identification of new targets for immunotherapy of ovarian adenocarcinoma based on the immunopeptidome of tumor cells
BACKGROUND. Ovarian adenocarcinoma is characterized by a high mortality rate due to late diagnosis and the development of resistance to standard chemotherapy. Despite the introduction of targeted therapies, the risk of recurrence remains high, highlighting the need for new therapeutic approaches. In this view, immunotherapy is a promising approach, but requires the identification of specific tumor antigens. AIM. To identify tumor antigens in ovarian adenocarcinoma that are promising for immunotherapy. METHODS. Immunopeptidome from cell lines and postoperative material of patients with ovarian adenocarcinoma were isolated using immunoaffinity chromatography followed by liquid chromatography-mass spectrometry analysis. RESULTS. In this study, we tested an affinity chromatography-based immunopeptidome isolation protocol, comparing various detergents (CHAPS, NP-40, SOD, and Triton X-100) for cell lysis, and observed no statistically significant differences in the number of identified peptides. Using NP-40, 5 peptides belonging to the proteins of cancer/testis antigens (CTA) were identified in the immunopeptidomes of postoperative material from patients with ovarian adenocarcinoma, 3 of which, according to the human protein atlas, are indeed not expressed in normal ovarian tissues. CONCLUSION. Each of the four tested detergents provides identification of unique sets of peptides. Immunopeptidome analysis allows the identification of peptides ofCTA proteins, but a larger sample of postoperative material from patients with ovarian adenocarcinoma and experimental testing of the immunogenicity of the identified peptides are needed for further research.
2026-04-01 | Overexpression of the erythropoietin receptor is associated with upregulation of tubulin beta 6 and paclitaxel resistance in ovarian adenocarcinoma cells.
The emergence of tumor cell resistance is one of the major issues in current oncology practice. It reduces the effectiveness of therapy and worsens cancer patients' prognoses. However, it confirms a wide range of molecular interactions as well as the complexity of the human organism. Our previous research confirmed the functionality of the erythropoietin receptor (EPOR) in ovarian and breast cancer cells, as well as its relationship to these cells' sensitivity to specific therapies. The current study demonstrates that EPOR overexpression in human ovarian adenocarcinoma cells A2780 is directly linked to paclitaxel resistance. Furthermore, EPOR overexpression results in morphological changes that vary according to the pattern of EPOR isotypes expressed. In this regard, the most interesting result appears to be the change in the shape of the T clone, which has a tendency to form spheroidal structures. In addition, functional enrichment analysis demonstrated that EPOR-associated differentially expressed genes are involved in several biological and cell processes. Indeed, a T clone with a single 68 kDa EPOR isotype demonstrates significant resistance to paclitaxel therapy and is associated with the upregulation of tubulin beta 6.
oligonucleotides
2025-11-19 | Long non-coding RNA HCP5 accelerated malignant progression of ovarian cancer by inhibiting ferroptosis through interaction with polypyrimidine tract binding protein 1.
Ovarian cancer (OVCA) is the third most common gynaecological malignancy worldwide. Long non-coding RNA (LncRNA) HCP5 and polypyrimidine tract binding protein 1 (PTBP1) involved in regulating tumors, however, with undefined mechanism in OVCA. After validating lentiviral transfection efficiency, OVCA mouse models were constructed by intraperitoneal injection of ID8-Luc cells for 8 weeks, with sh-lncRNA HCP5, oe-PTBP1, and ferroptosis agonist Erastin treatment. In vivo imaging, tumor metastasis, immunohistochemistry, HE, and TUNEL staining were performed. Human ovarian adenocarcinoma cell SKOV3 cells underwent the same grouping. Interaction between lncRNA HCP5 and PTBP1 was examined using RNA immunoprecipitation and RNA pull-down assay. CCK8, flow cytometry, transmission electron microscopy, biochemical kits, qRT-PCR, and Western blot were performed. In OVCA mice, sh-lncRNA HCP5 inhibited tumor growth and increased tumor tissue pathological damage and apoptosis, with lower PTBP1, Ki67, and B-cell lymphoma-2 (Bcl-2) expression, and higher Bcl-2 associated X and caspase-3 expression. Meanwhile, sh-lncRNA HCP5 induced ferroptosis, with reduced glutathione peroxidase 4, glutathione, and recombinant solute carrier family 7, member 11 expression, and elevated malondialdehyde, lipid peroxides, 4-hydroxynonenoic acid, acyl-CoA synthetase long chain family member 4, and transferrin receptor protein expression. These effects were reversed by oe-PTBP1, and Erastin weakened the pro-tumor role of oe-PTBP1, which were also observed in SKOV3 cells. Additionally, in vitro, lncRNA HCP5 was confirmed to bind to PTBP1, and sh-lncRNA HCP5 reduced cell viability and enhanced reactive oxygen species. LncRNA HCP5 may promote OVCA progression by inhibiting ferroptosis through interaction with PTBP1, providing new targets in OVCA treatment.
2025-10-14 | Fe 3 O 4 @Au loaded with PNPO-siRNA for the diagnosis and treatment of ovarian cancer
Aim To design and fabricate composite magnetic nanoparticles (MNPs), Fe3O4@Au(Cy5.5)-DOPE/PNPO-siRNA, for the diagnosis and treatment of ovarian cancer (adenocarcinoma cells).Materials and methods Fe3O4@Au(Cy5.5)-DOPE/PNPO-siRNA nanoparticles were synthesized using seed growth and chemical reduction methods. The fabricated Fe3O4@Au nanoparticles were systematically characterized and evaluated. For in vitro studies, the anti-tumor effects were assessed in naturally resistant SKOV3 ovarian adenocarcinoma cells. Cellular uptake, gene-silencing efficiency, and cytotoxicity assays were conducted to determine their therapeutic potential. For in vivo studies, a xenograft mouse model harboring SKOV3 tumors was established to evaluate magnetic resonance imaging (MRI) contrast enhancement and biosafety of nanoparticles. MRI was performed using T2-weighted imaging (T2WI) to monitor tumor accumulation and signal changes. The biosafety was further examined through histopathological analysis of major organs.Results We successfully designed and fabricated Fe3O4@Au composite magnetic nanoparticles (MNPs) encapsulated with surface lipids, which exhibited excellent biocompatibility and safety. These Fe3O4@Au composite MNPs effectively delivered PNPO-siRNA into SKOV3 cells, enabling both ovarian cancer treatment and MRI. In vivo MRI of SKOV3 tumor-bearing mice showed effective tumor accumulation of nanoparticles. T2WI revealed a peak signal reduction of approximately 17% at 3h post-injection (ANOVA, compared to the pre-injection group, ***p < 0.001), followed by gradual recovery over time. These findings indicate that Fe3O4@Au MNP can serve as effective negative MRI contrast agent to enhance ovarian cancer detection. For therapeutic evaluation, Fe3O4@Au(Cy5.5)-DOPE/PNPO-siRNA nanoparticles significantly inhibited SKOV3 cell proliferation in vitro. Furthermore, biosafety assessments demonstrated no significant toxicity in major organs, supporting their potential for as a safe and effective platform for the treatment of ovarian cancer.Conclusion Fe3O4@Au(Cy5.5)-DOPE/PNPO-siRNA composite magnetic MNPs demonstrate significant potential as dual-function agents, serving both as MRI tracers and as molecular therapeutic platforms for ovarian cancer in vivo.
2024-06-06 | The consequences of manipulating relaxin family peptide receptor 1 (RXFP1) level in ovarian cancer cells.
Deregulation of the relaxin family peptide system (RFPS) appears to increase the risk of range of cancers, including epithelial ovarian cancers (EOC). The present study examines the effect of relaxin family peptide receptor 1 (RXFP1) level on the biological properties of human epithelial ovarian adenocarcinoma cells (OVCAR4 and SKOV3). RXFP1 was downregulated (RXFP1↓) in the cells using the RXFP1 sgRNA CRISPR All-in-One Lentivirus set (pLenti-U6-sgRNA-SFFV-Cas9-2A-Puro), and upregulated (RXFP1↑) using the RXFP1 CRISPRa sgRNA Lentivector (pLenti-U6-sgRNA-PGK-Neo) kit, which activates the RXFP1 gene when paired with dCas9-SAM. The changes taking place during adhesion to extracellular matrix (ECM) proteins were assessed in multi-well plates coated with collagen, fibronectin, laminin and gelatin. Cellular viability was monitored based on mitochondrial metabolic activity (MTT Assay, Alamar Blue Assay) and adenosine triphosphate production (ATP Assay). The rate of cell proliferation was determined based on the percentage of Ki67 immunoreactive cells and the numbers of cells in particular cell-cycle phases. The mesenchymal-like (Boyden Chamber Assay) and amoeboid-like movements (Wound Healing Assay) of ovarian cancer cells were also analyzed after transfection. RXFP1 downregulation decreased the adhesion properties of ovarian cancer cells and increased the tendency for apoptosis under stressful conditions. In contrast, RXFP1 upregulation had pro-proliferative, pro-survival and promigratory effects. Our findings confirm that the relaxin-2/RXFP1 signaling pathway plays a role in the promotion of growth and progression of ovarian cancer.
2024-03-19 | High expression levels of centromere protein O participates in cell activity of human ovarian cancer
Abstract Ovarian cancer is a common malignant tumor in women, with a high mortality rate ranking first among gynecological tumors. Currently, there is insufficient understanding of the causes, pathogenesis, recurrence and metastasis of ovarian cancer, and early diagnosis and treatment still face great challenges. The sensitivity and specificity of existing ovarian cancer screening methods are still unsatisfactory. Centromere protein O (CENP-O) is a recently discovered structural centromere protein that is involved in cell death and is essential for spindle assembly, chromosome separation, and checkpoint signaling during mitosis. The abnormal high expression of CENP-O was detected in various tumors such as bladder cancer and gastric cancer, and it participates in the regulation of tumor cell proliferation. In this study, we detect the expression abundance of CENP-O mRNA in different ovarian cancer cells ( ES-2, A2780, Caov-3, OVCAR-3 and SK-OV-3). The biological function changes of cell proliferation and apoptosis were detected and the role of CENP-O in ovarian cancer cell proliferation and apoptosis was explored by knocking down the expression of CENP-O gene. The results showed that CENP-O gene was significantly expressed in 5 types of ovarian cancer cell lines. After knocking down the CENP-O gene, the proliferation and cloning ability of ovarian cancer cells decreased, and the apoptosis increased. This study indicates that CENP-O has the potential to be a molecular therapeutic target, and downregulating the expression of CENP-O gene can break the unlimited proliferation ability of cancer cells and promote their apoptosis, providing a foundation and new ideas for subsequent molecular mechanism research and targeted therapy.
2023-07-20 | ZFP57 promotes ovarian cancer progression by transcriptionally regulating BRCA1 and managing G1 checkpoint
Ovarian cancer (OC) which is one of the frequently-occurring gynecologic malignant tumors, endangers the health of women. The zinc finger protein 57 (ZFP57) plays crucial functions during the progression of cancer and is reported as a prognostic and therapeutic candidate in a variety of cancer. However, the biological function as well as the underlying mechanism of ZFP57 during OC progression remains unknown. Here, ZFP57 expression was found prominently increased in OC tissues and correlated with the prognosis of OC patients. Knock down of ZFP57 in OC cells inhibited the cell proliferation and migration, and also arrested the cells at G1 phase as well as accelerated the apoptosis. Additionally, ZFP57 transcriptionally regulated BRCA1 expression in OC, indicating that ZFP57 may affect BRCA1 mediated G1 checkpoint to regulate the cell cycle of OC cells and further influence the progression of OC. Taken together, our present study discovered a novel function of ZFP57 in OC, suggesting that ZFP57 could be potentially treated as a prognostic biomarker and therapeutic target for OC patients.
other
2026-04-21 | Intraperitoneal administration of NK-92 improves survival in xenografts of early and established ovarian cancer models.
Ovarian cancer (OC) is a leading cause of gynecological cancer-related mortality. Management remains challenging as the disease frequently presents with intra-abdominal metastases at diagnosis, standard therapies can be associated with severe complications and disease recurrence is common. While cellular immunotherapy is increasingly investigated as a promising approach, the most effective routes of administration need to be established. We have investigated NK cell therapeutics as a less toxic option and examined the permanent NK cell line, NK-92, as a suitable model. Here, we report two xenograft mouse models with the ovarian adenocarcinoma cell line, SKOV-3, representing early-stage OC and late-stage OC with ascites to comprehensively evaluate the anti-cancer efficacy of different routes of NK-92 administration. Bioluminescence imaging, cell tracking with the IVIS system and animal survival were used to evaluate outcomes. The cells were administered via intraperitoneal (IP), intravenous (IV), or a combination of IP and IV routes. We showed that NK-92 significantly increased animal survival when delivered IP (p = 0.009 and p = 0.018) or combined IP and IV (p = 0.05 and p = 0.017) in early and established OC xenografts, respectively, whereas intravenous delivery at similar doses had no effect on survival (p = 0.665 and p = 0.052) compared with untreated controls. These findings, and our novel models, have potential implications for enhancing the clinical benefit of NK therapy in patients with advanced OC.
2025-03-05 | CRISPR-Cas9 knockout of DGKα/ζ improves the anti-tumor activities of TAG-72 CAR-T cells in ovarian cancer
High recurrence and chemoresistance in solid tumors, like ovarian cancer, stress the need for new therapies. Chimeric antigen receptor (CAR)-T cells show promise but face challenges due to tumor heterogeneity and immune suppression in the tumor microenvironment (TME). Thus, novel approaches are needed to further enhance the efficacy of CAR-T cell therapies. In T cell therapies, inhibiting checkpoint molecules is crucial for overcoming exhaustion and boosting anti-tumor activity. Additionally, prioritizing safety by engineering cells to target markers absent on normal healthy cells reduces off-target risks. We targeted tumor-associated glycoprotein 72 (TAG-72), an oncofetal antigen highly expressed in adenocarcinomas like ovarian cancer, by engineering TAG-72 CAR-T cells and used CRISPR-Cas9 to knock out the T cell-inhibitory enzymes diacylglycerol kinase (DGK) α and ζ. DGKα/ζ knockout (KO) did not impact CAR-T cell viability or phenotype. These cells selectively killed TAG-72-expressing cancer cells in vitro and ablated established tumors in vivo for up to 100 days, whereas non-deleted control TAG-72 CAR-T cells showed tumor relapse around 40 days. These findings highlight the potential of CRISPR-induced DGKα/ζ KO to enhance CAR-T cell efficacy against solid tumors such as ovarian cancer, offering a promising avenue for improved cancer therapies.
2024-06-01 | Phase I/II study of TROP2 CAR engineered IL15-transduced cord blood-derived NK cells delivered intraperitoneally for the management of platinum resistant ovarian cancer, mesonephric-like adenocarcinoma, and pancreatic cancer.
TPS5626 Background: Novel treatments are needed for patients with ovarian, pancreatic, and mesonephric-like adenocarcinoma (MLA) that has recurred or progressed after initial treatment, as current standard of care therapies in these settings result in low response rates. Chimeric antigen receptor-transduced natural killer (CAR-NK) cells have emerged as a therapeutic alternative to CAR-T cells, with decreased toxicity and enhanced feasibility as an “off-the-shelf” therapy. TROP2, or trophoblast cell-surface antigen 2, is a transmembrane calcium-signal transducer that is overexpressed in many cancer types and associated with poor clinical outcomes. Recent studies have demonstrated TROP2 as a promising target for adoptive cell therapy in breast and gastric cancers. An intraperitoneal route of adoptive cell therapy delivery may provide superior disease control and decreased toxicity in these target cancers with predisposition for intra-abdominal/peritoneal involvement. Pre-clinical studies have established the efficacy and safety of TROP2 CAR NK cells in ovarian and pancreatic cancers. Methods: This is a phase I/II study of the intraperitoneal delivery of TROP2-CAR/IL-15 transduced cord blood (CB)-NK cells for recurrent/progressive ovarian cancer, pancreatic cancer, and MLA (NCT05922930). Subjects must have disease present in the peritoneal cavity or retroperitoneal lymph nodes and tumors must demonstrate at least 1+ TROP2 expression by immunohistochemistry. The primary endpoints are toxicity rates and defining the recommended phase II dose (RP2D). Key secondary endpoints include treatment efficacy, circulating tumor DNA levels, serial characterization of the immune microenvironment, and patient-reported outcomes. There are four possible dose levels ranging from 8.0x10 6 to 4.0x10 9 cells. We will enroll patients from the three disease cohorts using the Bayesian optimal interval (BOIN) design to find the maximum tolerated dose and RP2D, with a maximum sample size of 21. Once the R2PD is chosen, we will enroll up to 10 patients within each disease cohort to further evaluate safety and efficacy. Subjects enrolled will be admitted to the hospital, receive lymphodepleting chemotherapy (fludarabine 30 mg/m 2 and cyclophosphamide 300mg/m 2 ) on days -5 to -3, and will receive a single dose of cryopreserved and thawed intraperitoneal TROP2-CAR/IL15-transduced CB-NK cells on day 0. The dose-limiting toxicity window will be from day 0 until day 28. Severity of adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5. The first patient on this trial was treated in January 2024. Clinical trial information: NCT0592293 .
2024-04-30 | Comprehensive Bioinformatic Investigation of TP53 Dysregulation in Diverse Cancer Landscapes
P53 overexpression plays a critical role in cancer pathogenesis by disrupting the intricate regulation of cellular proliferation. Despite its firmly established function as a tumor suppressor, elevated p53 levels can paradoxically contribute to tumorigenesis, influenced by factors such as exposure to carcinogens, genetic mutations, and viral infections. This phenomenon is observed across a spectrum of cancer types, including bladder (BLCA), ovarian (OV), cervical (CESC), cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), diffuse large B-cell lymphoma (DLBC), esophageal carcinoma (ESCA), head and neck squamous cell carcinoma (HNSC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and uterine corpus endometrial carcinoma (UCEC). This broad spectrum of cancers is often associated with increased aggressiveness and recurrence risk. Effective therapeutic strategies targeting tumors with p53 overexpression require a comprehensive approach, integrating targeted interventions aimed at the p53 gene with conventional modalities such as chemotherapy, radiation therapy, and targeted drugs. In this extensive study, we present a detailed analysis shedding light on the multifaceted role of TP53 across various cancers, with a specific emphasis on its impact on disease-free survival (DFS). Leveraging data from the TCGA database and the GTEx dataset, along with GEPIA, UALCAN, and STRING, we identify TP53 overexpression as a significant prognostic indicator, notably pronounced in prostate adenocarcinoma (PRAD). Supported by compelling statistical significance (
2024-03-17 | CD40 stimulation via CD40 ligand enhances adenovirus‐mediated tumour immunogenicity including ‘find‐me’, ‘eat‐me’, and ‘kill‐me’ signalling
Abstract Immunostimulatory gene therapy using oncolytic viruses is currently evaluated as a promising therapy for cancer aiming to induce anti‐tumour immunity. Here, we investigate the capacity of oncolytic adenoviruses (LOAd) and their transgenes to induce immunogenicity in the infected tumour cells. Oncolysis and death‐related markers were assessed after infection of eight human solid cancer cell lines with different LOAd viruses expressing a trimerized, membrane‐bound (TMZ)‐CD40L, TMZ‐CD40L and 41BBL, or no transgenes. The viruses induced transgene expression post infection before they were killed by oncolysis. Death receptors TRAIL‐R1, TRAIL‐R2 and Fas as well as immunogenic cell death marker calreticulin were upregulated in cell lines post infection. Similarly, caspase 3/7 activity was increased in most cell lines. Interestingly, in CD40 + cell lines there was a significant effect of the TMZ‐CD40L‐encoding viruses indicating activation of the CD40‐mediated apoptosis pathway. Further, these cell lines showed a significant increase of calreticulin, and TRAIL receptor 1 and 2 post infection. However, LOAd viruses induced PD‐L1 upregulation which may hamper anti‐tumour immune responses. In conclusion, LOAd infection increased the immunogenicity of infected tumour cells and this was potentiated by CD40 stimulation. Due to the simultaneous PD‐L1 increase, LOAd viruses may benefit from combination with antibodies blocking PD1/PD‐L1.
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Drug Discovery Landscape
1 orphan drug designation for Adenocarcinoma of ovary, including 1 approved therapy.
1 orphan drug designation for Adenocarcinoma of ovary, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Altretamine [Hexalen] | small molecules | FDA | 1984-02-09 | 1990-12-26 | Medimmune Oncology, Inc. |
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