RARE DISEASE
Yolk sac tumor
Yolk sac tumor
Yolk sac tumor
Synonyms: Endodermal sinus tumor
Synonyms: Endodermal sinus tumor
Synonyms: Endodermal sinus tumor
Drug discovery
1
drug
With orphan designation
Overview
Yolk sac tumor (YST) is a rare, aggressive germ cell malignancy arising from pluripotent cells, most commonly in gonads (ovaries/testes) or extragonadal sites (mediastinum, liver). It predominantly affects children and young adults, with elevated serum AFP serving as a key diagnostic marker. Treatment combines fertility-sparing surgery (where feasible) and cisplatin-based chemotherapy (BEP regimen), achieving >90% 5-year survival in early stages. Advanced disease carries poorer outcomes (51–71% survival) [7][19][11].
Burden
Aggressive biology: Rapid growth, early metastasis (62% lymph nodes, 41% lungs) [1][9].
Stage-dependent survival: 94.8% 5-year survival for stage I vs. 51.6% for stage IV [19][9].
Treatment toxicity: BEP chemotherapy risks pulmonary/renal toxicity and infertility [11][18]. Fertility preservation is prioritized in 58% of ovarian YST cases [19][13].
Therapies
Fertility-sparing surgery (e.g., unilateral oophorectomy) + BEP chemotherapy (bleomycin, etoposide, cisplatin) [1][3][19].
Neoadjuvant chemotherapy for bulky/advanced tumors to enable less invasive resection [3][5][16].
Post-treatment surveillance: serial AFP monitoring and imaging to detect recurrence [11][13].
Categories: rare neoplastic diseases, rare transplant-related disorders
Research Papers
839 drug discovery papers about Yolk sac tumor, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
839 drug discovery papers about Yolk sac tumor, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-16 | Yolk Sac Tumor of Cervix in a Toddler - A Very Rare Case Scenario
BackgroundYolk sac tumor is a rare malignant germ cell tumor that commonly occurs in the ovaries and testes of young patients.Primary cervical yolk sac tumor is extremely rare, with very few cases reported in young children.
2026-08-31 | Complete radiological and biochemical remission at 26 months in a young adult with primary mediastinal yolk sac tumor: a case report and literature review on multimodal management
Abstract Background Primary mediastinal yolk sac tumor (PMYST) is an extremely rare and highly malignant germ cell tumor that predominantly affects young males and is associated with a poor prognosis. Case presentation We present the case of a 23-year-old non-smoking male diagnosed with stage III (cT4N0M0) PMYST who received comprehensive treatment guided by a multidisciplinary team (MDT). The treatment regimen included 5 cycles of neoadjuvant chemotherapy with BEP (bleomycin, etoposide, and cisplatin), followed by radical surgery, postoperative radiotherapy, and 4 cycles of adjuvant chemotherapy. Post-treatment, the patient's serum tumor markers normalized, with a partial radiological response (PR) and sustained biochemical remission. As of the latest follow-up in August 2025 (26 months after diagnosis), the patient remains in complete radiological and biochemical remission with no signs of recurrence. Conclusions This case demonstrates that an intensive MDT-guided multimodal approach incorporating aggressive neoadjuvant chemotherapy, radical surgery, and consolidative sequential radiotherapy and chemotherapy may lead to encouraging outcomes, including the achievement of complete radiological and biochemical remission documented at 26 months. However, this case is more reflective of individualized treatment for a specific patient, and it also highlights the need for intensified surveillance beyond two years.
2026-07-09 | Laparoscopic Surgery for Pediatric Malignant Ovarian Germ Cell Tumors After Neoadjuvant Chemotherapy: A Single-Center Retrospective Study
Purpose: The purpose of this study was to evaluate the clinical effects and safety for cancer treatment of neoadjuvant chemotherapy (NACT) when combined with laparoscopic fertility-sparing (anatomical preservation) surgery in pediatric patients who have large malignant ovarian germ cell tumors (MOGCTs). Methods: We performed a retrospective analysis on seven young female patients with a median age of 8.8 years (range: 10 months to 13.4 years). The patients were treated between 2015 and 2023, and all of them received two to three cycles of JEB (carboplatin, etoposide, and bleomycin) regimen as NACT. After the NACT, these patients had laparoscopic (n = 7) unilateral salpingo-oophorectomy. Results: Neoadjuvant chemotherapy (NACT) achieved a median reduction in tumor volume of 91% (range: 85% to 97%). All the procedures were completed successfully and there was no need to convert to open surgery. The median operative time was 85 min (range: 70 to 120 min), and the blood loss was minimal. The median blood loss was 10 mL, with a range of 5 to 50 mL. In patients with yolk sac tumors, alpha-fetoprotein (AFP) levels returned to normal within a median of 20 days after the operation. With a median follow-up of 54 months (range: 18 to 118 months), all the patients had 100% disease-free survival. Conclusions: This study suggests that NACT combined with laparoscopic fertility-sparing (anatomical preservation) surgery may be effective and appears promising for selected pediatric patients with MOGCTs.
2026-06-22 | Primary Yolk Sac Tumor of the Endometrium: A Case Report and Comprehensive Literature Review.
Yolk sac tumor (YST) of the endometrium is very rare, with fewer than 40 cases reported in the English literature. We here describe a case of primary endometrial YST and discuss the clinicopathological features with a literature review. A 66-year-old Chinese woman presented with abnormal vaginal bleeding for 15 days and a uterine mass for 3 days. The preoperative alpha-fetoprotein (AFP) level was 9652.0 ng/mL, while other serum tumor markers, including carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and β-human chorionic gonadotropin (β-HCG), were 40.2 ng/mL, 29.19 ng/mL, and 27.7 mIU/mL, respectively. Pelvic ultrasound imaging revealed a 7.1 × 6.6 × 6.0 cm mass in the endometrial cavity. The patient underwent total abdominal hysterectomy, salpingo-oophorectomy, and partial omental resection. The morphologic and immunohistochemical pattern (cytokeratin+++, Sal-Like Protein 4+++, AFP++, Focal Hepatocyte Nuclear Factor 1 beta+, and Focal Glypican-3+) was consistent with a primary YST of the endometrium, and the final pathologic stage was IVb based on the International Federation of Gynecology and Obstetrics (FIGO) staging. Postoperative serum AFP level was 5193.0 ng/mL 5 days after the operation. Primary endometrial YST is extremely rare. It should be differentially diagnosed from other uterine malignancies. Complete surgical staging combined with chemotherapy may have a better survival impact on endometrial YST.
2026-06-19 | Hemorrhagic Brain Tumor As the Initial Presentation of Metastatic Testicular Yolk Sac Tumor: A Case Report and Review of the Literature.
Yolk sac tumors (YSTs) are highly malignant germ cell neoplasms, most commonly arising in the gonads. Intracranial involvement is exceptionally rare and typically affects the pineal or suprasellar regions. Metastatic YST presenting as a hemorrhagic brain lesion is an exceedingly unusual occurrence that poses significant diagnostic and therapeutic challenges. We report the case of a 26-year-old male who presented with rapidly progressive left-sided weakness and headache. Imaging revealed a right frontoparietal hemorrhagic mass with marked vasogenic edema and midline shift. The patient underwent urgent right frontal craniotomy and near-total tumor excision via a transsulcal approach. Postoperatively, neurological recovery was rapid, with near-complete motor improvement within days. Systemic evaluation revealed multiple pulmonary and para-aortic metastases and an enlarged right testis. Serum α-fetoprotein (AFP) was markedly elevated, and histopathological examination confirmed the diagnosis of YST. The patient received adjuvant chemotherapy, followed by radical orchidectomy and lymph node dissection, achieving normalization of AFP and full functional recovery at one year of follow-up. This case underscores the importance of considering germ cell tumors in the differential diagnosis of hemorrhagic brain lesions, particularly in young males. Early surgical intervention, combined with systemic chemotherapy, can lead to favorable neurological and oncologic outcomes even in such rare and aggressive presentations.
antibodies
2026-06-08 | Pembrolizumab Failure in an Aggressive, Platinum-Resistant Primary Mediastinal Yolk Sac Tumor With Rapid Metastatic Dissemination, Spinal Cord Compression, and a Fatal Outcome.
Primary mediastinal yolk sac tumors are rare, aggressive extragonadal nonseminomatous germ cell tumors that carry a poorer prognosis than their gonadal counterparts. Outcomes are particularly dismal in platinum-resistant disease, and the role of immune checkpoint inhibitors in this setting remains poorly defined. We report the case of a 26-year-old man with a primary mediastinal yolk sac tumor who progressed despite multimodal therapy, including etoposide, ifosfamide, and cisplatin chemotherapy, high-dose carboplatin and etoposide with autologous stem cell transplantation, gemcitabine and paclitaxel, surgical debulking, and radiation therapy. Pembrolizumab was initiated for progressive disease; however, treatment was associated with rapid biochemical progression, with alpha-fetoprotein doubling from 44,053 to 90,123 ng/mL over two months, accompanied by radiographic worsening of mediastinal, chest wall, and osseous metastases. Shortly thereafter, he developed acute bilateral lower extremity weakness and urinary retention. Magnetic resonance imaging demonstrated new and enlarging multifocal spinal metastases with severe epidural extension and spinal canal stenosis, including recurrence within a prior laminectomy bed and new cervical involvement. Despite palliative radiation, he remained paraplegic and experienced continued systemic progression with central nervous system dissemination. No further disease-directed therapies were available, and he ultimately died from progressive metastatic disease. This case highlights the aggressive biology of platinum-resistant primary mediastinal yolk sac tumors, illustrates primary resistance to programmed death-1 inhibition, and underscores the urgent need for more effective salvage strategies in this high-risk population.
2026-05-28 | Expression of nectin-4 in germ-cell tumors.
e17009 Background: Nectin-4 is a cell adhesion molecule and therapeutic target in several malignancies, including urothelial carcinoma. However, its expression pattern in germ cell tumors (GCT) remains poorly characterized. Given the limited treatment options for refractory GCTs, and the urgent need for novel therapeutic options, we present a retrospective analysis of Nectin-4 expression on pathology samples from patients with GCT. Methods: Samples from 93 unique patients with GCT from Indiana University Simon Comprehensive Cancer Center from 2010-2022 were identified. Patients with both seminoma and non-seminoma were included. Nectin-4 staining was performed by IQVIA Laboratories using the non-commercially available anti-Nectin-4 antibody (clone M22-312B41.1). Results: Overall, 93 samples were identified, 5 subjects did not have sufficient tissue to complete Nectin 4 testing. Of 88 evaluable samples, 43 (48.8%) demonstrated Nectin-4 expression. Expression varied significantly by histology. Teratoma demonstrated the highest prevalence, with 33 of 38 cases (86.8%) positive, with frequent high levels of expression (17 of 33 exhibiting ≥20% neoplastic cell positivity). Seminoma showed infrequent expression (3 of 29, 10.3%). No expression was observed in pure embryonal carcinoma (0 of 8). Yolk sac tumors demonstrated variable expression (3 of 7, 42.8%). Mixed histology tumors showed expression in 66% (4 of 6). Nectin-4 positivity was observed across multiple anatomic sites, including retroperitoneal lymph nodes (RP LN), lung, mediastinum, kidney, ureter, and other lymph nodes (LN) and metastatic locations. Conclusions: Nectin-4 varies across histology in GCT. Teratoma has the highest expression of Nectin-4 while embryonal carcinoma appears to have the lowest expression. Expression was not site restricted. These findings suggest that Nectin-4 may represent a biologically relevant therapeutic target especially in patients with unresectable teratoma. Nectin-4 expression by histologic subtype and anatomic site in germ cell tumors. Histology Nectin 4 expression (%) Sites All 43/88 (48.8%) Teratoma 33/38 (86.8%) RP LN (22)Lung (5)Mediastinum (3)Neck (1)Pelvic LN (1)Kidney (1) Seminoma 3/29 (10.3%) RP LN (2)Testis (1) Yolk Sac 3/7 (42.8%) RP LN (1)Ureter (1)Mediastinum (1) Embryonal Carcinoma 0/8 (0%) N/A Mixed Histology 4/6 (66.6%) Testis (1)RP LN (1)Mediastinum (2)
2026-05-22 | A Spotlight on Yolk-sac Tumors: Molecular Pathology, Current Diagnostics, and Novel Therapeutics.
Yolk-sac tumors are an aggressive subtype of testicular cancer that significantly contribute to disease progression and therapy resistance, especially in adults. While testicular cancer generally has high cure rates with cisplatin-based treatment, adult yolk-sac tumors often appear as components of mixed tumors with poor response to therapy and worse outcomes. Pediatric yolk-sac tumors tend to be pure and curable, but adult forms are biologically distinct and more aggressive. This review addresses the urgent clinical challenge posed by this disease by summarizing their pathophysiology, diagnostic biomarkers, and molecular drivers that sustain their aggressive behavior. By emphasizing key epigenetic and genetic alterations, as well as differentiation programs, this work highlights current and emerging therapeutic strategies aimed at improving early detection and treatment responses. Understanding yolk-sac tumor biology is essential to overcoming resistance and improving survival in patients affected by this high-risk tumor subtype.
2026-04-03 | Abstract 7220: Claudin-6 (CLDN6) expression is abundant in many different cancer entities
Abstract Claudin-6 (CLDN6) is a member of the claudin membrane protein family, which are crucial components of tight junctions, regulating paracellular permeability and maintaining cell polarity. CLDN6 is early expressed in embryonic stem cells and in specific fetal tissues such as kidney, lung, pancreas, and stomach, but is not expressed in corresponding adult tissues. While CLDN6 expression is largely lacking on normal tissues, it is highly expressed in several cancers. Therefore, CLDN6 is considered a potential therapeutic target. Studies evaluating CLDN6 as a target for monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, and CAR-T cells are underway. To better comprehend the prevalence of CLDN6 expression in different cancer types, CLDN6 was analyzed by immunohistochemistry (IHC) on tissue microarrays (TMAs) containing 4,464 samples from 101 different tumor types. A total of 39 tumor categories showed CLDN6 expression in at least one case, and 21 tumor categories contained at least one strongly positive case. At least weak CLDN6 positivity was most commonly seen in embryonal carcinoma (100%), seminoma (97.8%), and yolk sac tumor of the testis (97.6%), serous high-grade (76.4%), endometrioid (41.0%) and clear cell carcinoma (31.6%) of the ovary, carcinosarcoma of the ovary (66.7%) and the endometrium (36.0%), basal cell carcinoma of the skin (44.4%), adenocarcinoma of the ampulla Vateri (20%), endometrioid endometrial carcinoma (18.9%), adenocarcinoma of the cervix uteri (17.4%), adenocarcinoma of the esophagus (13.9%), gastric adenocarcinoma, intestinal type (11.6%), mucinous carcinoma of the ovary (9.1%), ductal adenocarcinoma of the pancreas (8.9%), muscle-invasive urothelial carcinoma (6.9%), cholangiocarcinoma (5.9%), squamous cell carcinomas of the esophagus (4.5%), vulva (4.3%), skin (4.1%), larynx (3.1%), penis (2.8%), pharynx (2.3%), anal canal (1.7%), oral cavity (1.2%), and the cervix uteri (1.2%), Brenner tumor of the ovary (3.6%), invasive breast carcinoma of no special type (3.5%), hepatocellular carcinoma (2.0%), gastric adenocarcinoma, diffuse type (1.8%), colorectal adenocarcinoma (1.7%), and diffuse large B cell lymphoma (1.0%). Our tumor cohorts were large enough to compare CLDN6 expression with tumor phenotype in ovarian, endometrial and pancreatic cancer. CLDN6 positivity was associated with advanced pT stage (p<0.0001) and high grade (p=0.0003) in ovarian cancer and with high grade in endometrial carcinoma (p=0.0179) but was unrelated to phenotype in pancreatic ductal adenocarcinoma. It is concluded that CLDN6 is expressed at significant levels in many different tumor types. Once anti-CLDN6 drugs are approved as safe and efficient, patients with many different cancer types may benefit from these new therapies. Citation Format: Veit Bertram, Anin Sharifi, Katharina Möller, Florian Lutz, Florian Viehweger, Christina Tsourlakis, Georgia Makrypidi-Fraune, Martina Kluth, Christian Bernreuther, Guido Sauter, Andreas H. Marx, Ronald Simon, Fiete Gehrisch, Nina Schraps, Stefan Steurer, Christoph Fraune, Viktoria Chirico, Clara von Bargen, Cosima Völkel, Morton Freytag, Natalia Gorbokon, Maximilian Lennartz, Eike C. Burandt, Anne Menz, Till Krech, Sarah Minner. Claudin-6 (CLDN6) expression is abundant in many different cancer entities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7220.
2025-11-14 | Partial Response to Sintilimab-Based Multimodal Therapy in a Refractory Primary Mediastinal Yolk Sac Tumor: A Case Report.
Primary mediastinal yolk sac tumor (PMYST) represents an extremely rare and highly aggressive germ cell malignancy with poor prognosis and limited therapeutic options. We report a 55-year-old male who presented with a large anterior mediastinal mass measuring 149 × 73 mm and significantly elevated serum alpha-fetoprotein (AFP) levels (>1210 ng/mL). Histopathological examination and immunohistochemical staining confirmed the diagnosis of PMYST. An interim response was observed after one cycle of etoposide-cisplatin chemotherapy given concurrently with radiotherapy. However, upon completion of the entire chemoradiotherapy course (radiotherapy plus three cycles of chemotherapy), the patient was found to have disease progression with an enlarging tumor burden. Subsequently, sintilimab-based chemo-immunotherapy was initiated, resulting in a partial response achieved after four cycles of treatment. At the most recent follow-up, the patient demonstrates sustained clinical stability with continued disease control. This case highlights the potential efficacy of PD-1 inhibitor-based combination therapy in refractory mediastinal yolk sac tumor (YST), which may provide a novel therapeutic strategy for managing this challenging malignancy.
cell therapies
2026-01-05 | Establishment of a Patient-Derived Xenograft Model of a Testicular Yolk Sac Tumor.
We have established a highly stable and reproducible patient derived xenograft model that exclusively and robustly retains the morphological, functional, and proliferative characteristics of human yolk sac tumor of the testis. This model might provide an invaluable in vivo platform for accelerating the discovery and validation of novel therapeutic strategies for this aggressive malignancy, with the ultimate aim of improving the prognosis for affected patients.
2025-05-10 | Human malignant ovarian germ cell tumor cell lines derived from peritoneal cytology retrieving from circulating tumor cell system.
Malignant ovarian germ cell tumor (MOGCT) is a rare neoplasm predominantly affecting adolescent and young adult females. Establishing personalized permanent tumor cell lines is crucial for understanding tumor behavior and optimizing precision treatment for these patients. We developed a novel procedure for isolating and culturing human MOGCT cells from peritoneal wash cytology using the circulating cell extraction technique (Labyrinthbiotech Co. LLC, LABYRINTHCE01, China). Peripheral blood and peritoneal washings were collected from 15 patients, including those with yolk sac tumor (n = 6), dysgerminoma (n = 2), immature teratoma (n = 5), and mixed germ cell tumor (n = 2). After washing and centrifugation, samples were processed using the labyrinth technique to achieve high-purity cell cultures. The isolated tumor cells were characterized by immunofluorescence microscopy and flow cytometry. Immunohistochemical analysis enabled specific discrimination from primary peritoneal human fibroblasts. Cultures were established from peritoneal cytology with cell densities ranging from 10² to 10⁵ cells per well, with 5 samples showing over 10⁵ cell growth, 3 samples over 10⁴ cell growth, and others at 10³ cell growth. The longest cell culture has been maintained for 18 generations. Short tandem repeat (STR) analysis of cultured cells confirmed their germ cell tumor origin. Preliminary assessments of chemosensitivity in cultured cells have been found to reflect similar clinical responses in the corresponding patients. The MOGCT cell lines derived from peritoneal washings using the circulating tumor cell chip represent the tumor characteristics. This method holds promise for functional studies on rare ovarian tumors and for evaluating chemo-sensitivity for potential therapeutic applications.
2023-02-13 | Immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR)-T cell therapy: Potential treatment options against Testicular Germ Cell Tumors
Germ cell tumors (GCTs) represent a heterogeneous neoplasm family affecting gonads and rarely occurring in extragonadal areas. Most of patients have a good prognosis, often even in the presence of metastatic disease; however, in almost 15% of cases, tumor relapse and platinum resistance are the main challenges. Thus, novel treatment strategies with both improved antineoplastic activity and minor treatment-related adverse events compared with platinum are really expected. In this context, the development and the high activity demonstrated by immune checkpoint inhibitors in solid tumors and, subsequently, the interesting results obtained from the use of chimeric antigen receptor (CAR-) T cell therapy in hematological tumors, have stimulated research in this direction also in GCTs. In this article, we will analyze the molecular mechanisms underlying the immune action in the development of GCTs, and we will report the data from the studies that tested the new immunotherapeutic approaches in these neoplasms.
2020-03-19 | Establishment and Characterization of a Novel Primitive Yolk Sac Tumour Cell Line, TC587.
Yolk sac tumour (YST) is a rare malignant ovarian germ cell tumour that often occurs in young women or adolescents and exhibits an unfavourable outcome. To evaluate the biological behavior of carcinomas in vitro, permanent tumour cell lines are required. However, previously, only a few human YST cell lines have been established. Therefore, we aimed to establish a novel YST cell line. We established a novel YST cell line, TC587, from an adolescent patient with ovarian YST. The cell line expressed AFP and SALL4, the characteristics of YST. In addition, we evaluated somatic mutations using next-generation sequencing and revealed some pathogenic variants, including mutations in the NRAS, KIT, KMT2C, RSF1, and TP53 genes. The newly established TC587 cell line may represent an effective tool for developing treatments and conducting molecular analyses for YST.
2019-12-18 | Salvage treatment for children with relapsed/refractory germ cell tumors: The Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) experience
Abstract Background Malignant germ cell tumors (GCTs) are a heterogeneous group of rare neoplasms in children. Optimal outcome is achieved with multimodal therapies for patients with both localized and advanced disease, especially after the introduction of platinum‐based chemotherapy regimens. In this respect, data on salvage treatment for children with relapsed or platinum‐refractory disease are still limited. Methods Retrospective analysis of data regarding patients affected by malignant GCTs with platinum‐refractory or relapsed disease after first‐line treatment according to AIEOP TCGM 2004 protocol was conducted. Results Twenty‐one patients, 15 females and 6 males, were considered for the analysis. All 21 patients received second‐line conventional chemotherapy (SLCT), two of these immediately after surgery for local relapse removal. Two patients showed a progression of disease during SLCT and died of disease shortly thereafter, whereas 19 patients were in partial remission (PR) or complete remission (CR) after SLCT. Treatment after SLCT consisted in surgery on residual tumor mass (9/19) followed by high dose of chemotherapy (HDCT) with autologous hematopoietic stem cell support (16/19). The overall survival (OS) and event‐free survival of the whole populations are 71% and 66.6%, respectively. Platinum‐refractory patients OS is 54.5% compared with 91.5% of the relapsed group. There were no treatment‐related deaths. Conclusion SLCT followed or not by HDCT is an effective salvage treatment for children with relapsed/refractory GCTs. However, the role of HDCT following SLCT needs to be further investigated, especially regarding the identification of specific patient subgroups, which can benefit from this more intensive treatment.
oligonucleotides
2023-11-27 | Testicular germ cell tumour cells release microRNA-containing extracellular vesicles that induce phenotypic and genotypic changes in cells of the tumour microenvironment.
Malignant germ-cell-tumours (GCTs) are characterised by microRNA (miRNA/miR-) dysregulation, with universal over-expression of miR-371~373 and miR-302/367 clusters regardless of patient age, tumour site, or subtype (seminoma/yolk-sac-tumour/embryonal carcinoma). These miRNAs are released into the bloodstream, presumed within extracellular-vesicles (EVs) and represent promising biomarkers. Here, we comprehensively examined the role of EVs, and their miRNA cargo, on (fibroblast/endothelial/macrophage) cells representative of the testicular GCT (TGCT) tumour microenvironment (TME). Small RNA next-generation-sequencing was performed on 34 samples, comprising representative malignant GCT cell lines/EVs and controls (testis fibroblast [Hs1.Tes] cell-line/EVs and testis/ovary samples). TME cells received TGCT co-culture, TGCT-derived EVs, and a miRNA overexpression system (miR-371a-OE) to assess functional relevance. TGCT cells secreted EVs into culture media. MiR-371~373 and miR-302/367 cluster miRNAs were overexpressed in all TGCT cells/subtypes compared with control cells and were highly abundant in TGCT-derived EVs, with miR-371a-3p/miR-371a-5p the most abundant. TGCT co-culture resulted in increased levels of miRNAs from the miR-371~373 and miR-302/367 clusters in TME (fibroblast) cells. Next, fluorescent labelling demonstrated TGCT-derived EVs were internalised by all TME (fibroblast/endothelial/macrophage) cells. TME (fibroblast/endothelial) cell treatment with EVs derived from different TGCT subtypes resulted in increased miR-371~373 and miR-302/367 miRNA levels, and other generic (eg, miR-205-5p/miR-148-3p) and subtype-specific (seminoma, eg, miR-203a-3p; yolk-sac-tumour, eg, miR-375-3p) miRNAs. MiR-371a-OE in TME cells resulted in increased collagen contraction (fibroblasts) and angiogenesis (endothelial cells), via direct mRNA downregulation and alteration of relevant pathways. TGCT cells communicate with nontumour stromal TME cells through release of EVs enriched in oncogenic miRNAs, potentially contributing to tumour progression.
2023-11-08 | Targeting oncogenic microRNAs from the miR-371~373 and miR-302/367 clusters in malignant germ cell tumours causes growth inhibition through cell cycle disruption.
MiR-371~373 and miR-302/367 cluster over-expression occurs in all malignant germ cell tumours (GCTs), regardless of age (paediatric/adult), site (gonadal/extragonadal), or subtype [seminoma, yolk sac tumour (YST), embryonal carcinoma (EC)]. Six of eight microRNAs from these clusters contain the seed sequence 'AAGUGC', determining mRNA targeting. Here we sought to identify the significance of these observations by targeting these microRNAs functionally. We targeted miR-371~373 and/or miR-302/367 clusters in malignant GCT cell lines, using CRISPR-Cas9, gapmer primary miR-302/367 transcript inhibition, and peptide nucleic acid (PNA) or locked nucleic acid (LNA)-DNA inhibition targeting miR-302a-d-3p, and undertook relevant functional assays. MiR-302/367 cluster microRNAs made the largest contribution to AAGUGC seed abundance in malignant GCT cells, regardless of subtype (seminoma/YST/EC). Following the unsuccessful use of CRISPR-Cas9, gapmer, and PNA systems, LNA-DNA-based targeting resulted in growth inhibition in seminoma and YST cells. This was associated with the de-repression of multiple mRNAs targeted by AAGUGC seed-containing microRNAs, with pathway analysis confirming predominant disruption of Rho-GTPase signalling, vesicle organisation/transport, and cell cycle regulation, findings corroborated in clinical samples. Further LNA-DNA inhibitor studies confirmed direct cell cycle effects, with an increase of cells in G0/G1-phase and a decrease in S-phase. Targeting of specific miR-371~373 and miR-302/367 microRNAs in malignant GCTs demonstrated their functional significance, with growth inhibition mediated through cell cycle disruption.
2023-03-30 | Supplementary Figures 1-12 from <i>LIN28</i> Expression in Malignant Germ Cell Tumors Downregulates <i>let-7</i> and Increases Oncogene Levels
<p>PDF - 492K, Supplementary Figure 1: Levels of the nine members of the let-7 family in pediatric malignant-GCTs. Supplementary Figure 2: PCR quantification of let-7e, LIN28 and LIN28B in malignant-GCTs.Supplementary Figure 3: Sylamer analysis of up-regulated genes in pediatric and adult malignant-GCTs. Supplementary Figure 4: Correlations between levels of let-7 and mRNA targets. Supplementary Figure 5: PCR quantification of HMGA2 in pediatric malignant-GCTs. Supplementary Figure 6: PCR validation of expression of selected let-7 mRNA targets in pediatric malignant-GCTs. Supplementary Figure 7: Effects of LIN28 depletion in malignant-GCT cells. Supplementary Figure 8: Independent confirmation of specific effects of LIN28 depletion in malignant-GCT cells. Supplementary Figure 9: Effects of let-7e mimic in malignant-GCT cells. Supplementary Figure 10: Relationships between MYCN and C-MYC versus LIN28 and LIN28B in malignant-GCTs. Supplementary Figure 11: MYCN depletion in malignant-GCTs (S11). Supplementary Figure 12: Schematic of the LIN28/let-7 axis in malignant-GCTs.</p>
2023-02-16 | Silencing of LINC00467 inhibits cell proliferation in testicular germ cell tumors cells Running Title: Silencing of LINC00467 regulates cell proliferation
Abstract Our previous study showed that LINC00467 expression decreased significantly in testicular germ cell tumors (TGCTs) compared with adjacent tissue. LINC00467 expression in TGCTs was upregulated at stages II/III compared with stage I, and was negatively correlated with the 5-year overall survival and 5-year disease-free survival. However, the role of LINC00467 in the development of TGCTs remains to be elucidated further. LINC00467 expression was silenced in the NCCIT and TCAM-2 cell lines using small interfering RNA (siRNA). The expression level of genes was validated using quantitative real-time polymerase chain reaction (qRT-PCR) analyses. The MTT and CCK8 assays were used to detect cell proliferation. The effects on cell cycle were evaluated using flow cytometry. Western blotting analysis was used to detect the expression level of proteins, while RNA-sequencing and bioinformatics methods were used to explore the mechanism of action of LINC00467 in TGCTs. The silencing of LINC00467 expression decreased cell proliferation, induced S phase arrest, and downregulated the cell cycle-related protein PCNA expression while upregulating the expression of P21. Dihydrotestosterone (DHT) stimulation experiments showed that DHT could upregulate the expression of LINC00467 and that the silencing of LINC00467 could reverse the effect of testosterone on cell proliferation. The Gene Set Enrichment Analysis (GSEA) showed that the P53 signaling pathway was associated with LINC00467. Our study reported that LINC00467 regulated cell proliferation and induced S phase arrest in TGCTs cells through the cell cycle-related proteins, PCNA, and P21. These enriched the mechanism of non-coding RNAs in the development of TGCTs.
2022-09-09 | Chromosome 3p25.3 Gain Is Associated With Cisplatin Resistance and Is an Independent Predictor of Poor Outcome in Male Malignant Germ Cell Tumors.
Cisplatin is the main systemic treatment modality for male type II germ cell tumors (GCTs). Although generally very effective, 5%-10% of patients suffer from cisplatin-resistant disease. Identification of the driving mechanisms of resistance will enable improved risk stratification and development of alternative treatments. We developed and characterized cisplatin-resistant GCT cell line models and compared their molecular characteristics with patient samples with cisplatin resistance and/or a poor clinical outcome. Subsequently, the association between the overlapping genetic features and clinical data was assessed. Finally, we used Cox regression to determine the prognostic relevance of these features within the currently used risk classification. Gain of chromosome 3p25.3 was detected in all cisplatin-resistant cell lines, and copy number of this region correlated with the level of resistance (R = 0.96, P = 1.5e-04). Gain of this region was detected at low frequencies in primary tumors and at higher frequencies in relapsed and/or cisplatin-resistant tumors. Chromosome 3p25.3 gain was associated with shorter progression-free survival and overall survival, with the strongest association observed in nonseminomas excluding pure teratomas. 3p25.3 gain was more frequently observed in tumors with yolk sac tumor histology and predicted adverse outcome independent of the International Germ Cell Cancer Collaborative Group risk classification and the presence of TP53/MDM2 alterations. On the basis of both in vitro analyses and clinical data, we found 3p25.3 to be strongly associated with cisplatin resistance and poor clinical outcome in male type II GCTs. Using genomic profiling, 3p25.3 status could help to improve risk stratification in male patients with type II GCT. Further characterization of this locus and underlying mechanisms of resistance is warranted to guide development of novel treatment approaches for cisplatin-resistant disease.
other
2026-09-18 | Intracardiac Metastasis From a Testicular Yolk Sac Tumor With Brain and Pulmonary Involvement: A Multimodality Management Case Report.
Cardiac metastasis from non-seminomatous germ cell tumors (NSGCTs) is exceedingly rare and represents an aggressive disease course. We report a 37-year-old man with a testicular yolk sac tumor who initially declined adjuvant therapy after orchiectomy. He later developed pulmonary metastases treated with BEP chemotherapy, followed by progressive disease with brain involvement requiring emergent decompressive craniectomy and whole-brain radiotherapy. Salvage TIP chemotherapy was administered. Persistent pulmonary disease led to thoracotomy, during which a discrete metastatic deposit in the right atrium was identified and surgically resected. Histopathology confirmed metastatic yolk sac tumor in all sites. The patient subsequently received maintenance therapy with oxaliplatin and bevacizumab. Follow-up has been based on clinical assessment and serial tumor marker monitoring, demonstrating ongoing biochemical and clinical stability for approximately 6 months following initiation of maintenance therapy, with the patient remaining on treatment at the time of this report. This case highlights the unpredictable metastatic behavior of NSGCTs and underscores the importance of multidisciplinary management in achieving disease control in rare and life-threatening metastatic presentations.
2024-03-11 | An unusual association of deletion of SMARCB1 in a patient with intracranial yolk sac tumor: A case-report
Deletion of SMARCB1/loss of INI is a well-known association in atypical rhabdoid teratoid tumors (ATRT) in the brain, rhabdoid tumors in the kidney, and less common tumors systemic tumors like sinonasal INI1 deficient carcinoma, gastric undifferentiated carcinoma, undifferentiated uterine sarcomas, and poorly differentiated chordomas. We describe homozygous deletion of the SMARCB1 gene in a patient diagnosed with pineal yolk sac tumor (YST), which is a rare entity. This association highlights the importance of INI1 staining when the clinical course is not progressing as expected and brings us to a critical management question: should this rare entity be treated more aggressively, like ATRT, versus the conventional approach to intracranial YST?
2024-02-27 | Overexpression of SerpinB9 in non-seminomatous germ cell tumors.
Serpinb9 is an inhibitor of granzyme B and is potentially involved in the immune escape of tumor cells. In the present study, bioinformatics analysis using open databases suggested that SerpinB9 is overexpressed in testicular embryonal carcinoma. Immunohistological analysis was performed on 28 cases of testicular germ cell tumors to investigate the relationship between SerpinB9 expression in testicular germ cell tumors and the tumor immune environment. SerpinB9 was significantly upregulated in the non-seminoma group and inversely correlated with the number of tumor-infiltrating CD8-positive cells. In addition, yolk sac tumors were characterized by the loss of human leukocyte antigen-class I expression. These findings suggest that SerpinB9 contributes to the immune escape of testicular germ cell tumors. Targeting therapy for SerpinB9 might therefore be useful in immunotherapy for testicular germ cell tumors resistant to immune checkpoint inhibitors.
2023-12-19 | Administration of a glypican-3 peptide increases the infiltration and cytotoxicity of CD8+ T cells against testicular yolk sac tumor, associated with enhancing the intratumoral cGAS/STING signaling.
Glypican-3 (GPC3) is highly expressed in testicular yolk sac tumor (TYST). GPC3 has been evaluated as a cancer vaccine for some types of tumors, but little is known on the effects of GPC3 peptide-based therapy on TYST. Here, we evaluated the antitumor effect of GPC3144-152 on TYST and its potential mechanisms. GPC3144-152 -specific CD8+ T cells were induced by vaccine immunization and examined by ELISPOT. The CD8+ T cells were purified for testing their cytotoxicity in vitro against TYST cells by CCK-8 and TUNEL assays and in vivo against tumor growth. The influence of GPC3144-152 loading and/or cGAS silencing on the tumor growth, apoptosis and cGAS/STING signaling was tested by immunohistochemistry, immunofluorescence, flow cytometry, and Western blot. Vaccination with GPC3144-152 induced tumor-specific CD8+ T cells that secreted high levels of IFN-γ and granzyme B, and had potent cytotoxicity against TYST in a dose-dependent manner. Adoptive transfer of CD8+ T cells and treatment with GPC3144-152 significantly inhibited the growth of TYST tumors, but less effective for cGAS-silenced TYST tumors in vivo. Treatment with GPC3144-152 enhanced the infiltration of CD8+ T cells into the tumor environment and their cytotoxicity against TYST tumors in vivo by up-regulating granzyme B and IFN-β expression, but down-regulating GPC3 expression in the tumors. Co-culture of CD8+ T cells with TYST in the presence of exogenous GPC3144-152 enhanced peptide-specific CD8+ T-cell cytotoxicity in vitro, accompanied by enhancing cGAS, γH2AX, TBK1, and IRF3 phosphorylation in TYST cells, but less effective in cGAS-silenced TYST cells. These data indicated that GPC3 peptide-specific CD8+ T cells had potent antitumor activity against TYST tumor, particularly for combined treatment with the peptide, which was partially dependent on the intratumoral cGAS/STNG signaling. GPC3 peptide vaccine may be valuable for the combination treatment of TYST.
2021-10-22 | Preservation of Fertility in a Patient with a Mixed Germ Tumor and Subsequent Successful Pregnancies. A Case Report
Objective:The objective of the study was to present the case of a patient with a diagnosis of a mixed germ cell tumor clinical stage (CS) IIC, who underwent conservative cytoreductive surgery and chemotherapy before initiation of a gonadotropin-releasing hormone agonist (GnRH-a) for fertility preservation, subsequently achieving spontaneous pregnancies.Material and methods: A 19-year-old patient underwent an examination for abdominal distention.Through clinical and imaging studies, an abdominal-pelvic mass of 15 cm × 14 cm × 10 cm was diagnosed with a location in the right ovary.After optimal cytoreductive surgery, the report confirmed a conservative germinal mixed tumor histopathology (80% endodermic sinuses and 20% embryonal carcinoma), CS IIC, so 4 cycles of chemotherapy were indicated.Before the start of and throughout the cytotoxic treatment, GnRH-a was administered.Results: At the end of the oncological treatment, a follicle stimulating hormone of 20 mUI/mL was reported, spontaneous resumption of menstrual cycles was presented 2 months after having concluded chemotherapy and suspended the use of GnRH-a.12 months later, a spontaneous pregnancy was normally achieved, which ended with a live newborn at 38.4 weeks of gestation, and 4 years later, a second spontaneous pregnancy, which also culminated in obtaining a healthy newborn.Conclusions: Fertility preservation should be considered a fundamental aspect of the quality of life of cancer survivors.Provided that there are no contraindications, the use of GnRH-a should be considered before the start of chemotherapy, remembering that this treatment could offer benefits beyond the preservation of fertility (bone, sexual, and cardiovascular health), providing comprehensive management.
small molecules
2026-09-16 | Yolk Sac Tumor of Cervix in a Toddler - A Very Rare Case Scenario
BackgroundYolk sac tumor is a rare malignant germ cell tumor that commonly occurs in the ovaries and testes of young patients.Primary cervical yolk sac tumor is extremely rare, with very few cases reported in young children.
2026-08-31 | Complete radiological and biochemical remission at 26 months in a young adult with primary mediastinal yolk sac tumor: a case report and literature review on multimodal management
Abstract Background Primary mediastinal yolk sac tumor (PMYST) is an extremely rare and highly malignant germ cell tumor that predominantly affects young males and is associated with a poor prognosis. Case presentation We present the case of a 23-year-old non-smoking male diagnosed with stage III (cT4N0M0) PMYST who received comprehensive treatment guided by a multidisciplinary team (MDT). The treatment regimen included 5 cycles of neoadjuvant chemotherapy with BEP (bleomycin, etoposide, and cisplatin), followed by radical surgery, postoperative radiotherapy, and 4 cycles of adjuvant chemotherapy. Post-treatment, the patient's serum tumor markers normalized, with a partial radiological response (PR) and sustained biochemical remission. As of the latest follow-up in August 2025 (26 months after diagnosis), the patient remains in complete radiological and biochemical remission with no signs of recurrence. Conclusions This case demonstrates that an intensive MDT-guided multimodal approach incorporating aggressive neoadjuvant chemotherapy, radical surgery, and consolidative sequential radiotherapy and chemotherapy may lead to encouraging outcomes, including the achievement of complete radiological and biochemical remission documented at 26 months. However, this case is more reflective of individualized treatment for a specific patient, and it also highlights the need for intensified surveillance beyond two years.
2026-07-09 | Laparoscopic Surgery for Pediatric Malignant Ovarian Germ Cell Tumors After Neoadjuvant Chemotherapy: A Single-Center Retrospective Study
Purpose: The purpose of this study was to evaluate the clinical effects and safety for cancer treatment of neoadjuvant chemotherapy (NACT) when combined with laparoscopic fertility-sparing (anatomical preservation) surgery in pediatric patients who have large malignant ovarian germ cell tumors (MOGCTs). Methods: We performed a retrospective analysis on seven young female patients with a median age of 8.8 years (range: 10 months to 13.4 years). The patients were treated between 2015 and 2023, and all of them received two to three cycles of JEB (carboplatin, etoposide, and bleomycin) regimen as NACT. After the NACT, these patients had laparoscopic (n = 7) unilateral salpingo-oophorectomy. Results: Neoadjuvant chemotherapy (NACT) achieved a median reduction in tumor volume of 91% (range: 85% to 97%). All the procedures were completed successfully and there was no need to convert to open surgery. The median operative time was 85 min (range: 70 to 120 min), and the blood loss was minimal. The median blood loss was 10 mL, with a range of 5 to 50 mL. In patients with yolk sac tumors, alpha-fetoprotein (AFP) levels returned to normal within a median of 20 days after the operation. With a median follow-up of 54 months (range: 18 to 118 months), all the patients had 100% disease-free survival. Conclusions: This study suggests that NACT combined with laparoscopic fertility-sparing (anatomical preservation) surgery may be effective and appears promising for selected pediatric patients with MOGCTs.
2026-06-22 | Primary Yolk Sac Tumor of the Endometrium: A Case Report and Comprehensive Literature Review.
Yolk sac tumor (YST) of the endometrium is very rare, with fewer than 40 cases reported in the English literature. We here describe a case of primary endometrial YST and discuss the clinicopathological features with a literature review. A 66-year-old Chinese woman presented with abnormal vaginal bleeding for 15 days and a uterine mass for 3 days. The preoperative alpha-fetoprotein (AFP) level was 9652.0 ng/mL, while other serum tumor markers, including carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and β-human chorionic gonadotropin (β-HCG), were 40.2 ng/mL, 29.19 ng/mL, and 27.7 mIU/mL, respectively. Pelvic ultrasound imaging revealed a 7.1 × 6.6 × 6.0 cm mass in the endometrial cavity. The patient underwent total abdominal hysterectomy, salpingo-oophorectomy, and partial omental resection. The morphologic and immunohistochemical pattern (cytokeratin+++, Sal-Like Protein 4+++, AFP++, Focal Hepatocyte Nuclear Factor 1 beta+, and Focal Glypican-3+) was consistent with a primary YST of the endometrium, and the final pathologic stage was IVb based on the International Federation of Gynecology and Obstetrics (FIGO) staging. Postoperative serum AFP level was 5193.0 ng/mL 5 days after the operation. Primary endometrial YST is extremely rare. It should be differentially diagnosed from other uterine malignancies. Complete surgical staging combined with chemotherapy may have a better survival impact on endometrial YST.
2026-06-19 | Hemorrhagic Brain Tumor As the Initial Presentation of Metastatic Testicular Yolk Sac Tumor: A Case Report and Review of the Literature.
Yolk sac tumors (YSTs) are highly malignant germ cell neoplasms, most commonly arising in the gonads. Intracranial involvement is exceptionally rare and typically affects the pineal or suprasellar regions. Metastatic YST presenting as a hemorrhagic brain lesion is an exceedingly unusual occurrence that poses significant diagnostic and therapeutic challenges. We report the case of a 26-year-old male who presented with rapidly progressive left-sided weakness and headache. Imaging revealed a right frontoparietal hemorrhagic mass with marked vasogenic edema and midline shift. The patient underwent urgent right frontal craniotomy and near-total tumor excision via a transsulcal approach. Postoperatively, neurological recovery was rapid, with near-complete motor improvement within days. Systemic evaluation revealed multiple pulmonary and para-aortic metastases and an enlarged right testis. Serum α-fetoprotein (AFP) was markedly elevated, and histopathological examination confirmed the diagnosis of YST. The patient received adjuvant chemotherapy, followed by radical orchidectomy and lymph node dissection, achieving normalization of AFP and full functional recovery at one year of follow-up. This case underscores the importance of considering germ cell tumors in the differential diagnosis of hemorrhagic brain lesions, particularly in young males. Early surgical intervention, combined with systemic chemotherapy, can lead to favorable neurological and oncologic outcomes even in such rare and aggressive presentations.
antibodies
2026-06-08 | Pembrolizumab Failure in an Aggressive, Platinum-Resistant Primary Mediastinal Yolk Sac Tumor With Rapid Metastatic Dissemination, Spinal Cord Compression, and a Fatal Outcome.
Primary mediastinal yolk sac tumors are rare, aggressive extragonadal nonseminomatous germ cell tumors that carry a poorer prognosis than their gonadal counterparts. Outcomes are particularly dismal in platinum-resistant disease, and the role of immune checkpoint inhibitors in this setting remains poorly defined. We report the case of a 26-year-old man with a primary mediastinal yolk sac tumor who progressed despite multimodal therapy, including etoposide, ifosfamide, and cisplatin chemotherapy, high-dose carboplatin and etoposide with autologous stem cell transplantation, gemcitabine and paclitaxel, surgical debulking, and radiation therapy. Pembrolizumab was initiated for progressive disease; however, treatment was associated with rapid biochemical progression, with alpha-fetoprotein doubling from 44,053 to 90,123 ng/mL over two months, accompanied by radiographic worsening of mediastinal, chest wall, and osseous metastases. Shortly thereafter, he developed acute bilateral lower extremity weakness and urinary retention. Magnetic resonance imaging demonstrated new and enlarging multifocal spinal metastases with severe epidural extension and spinal canal stenosis, including recurrence within a prior laminectomy bed and new cervical involvement. Despite palliative radiation, he remained paraplegic and experienced continued systemic progression with central nervous system dissemination. No further disease-directed therapies were available, and he ultimately died from progressive metastatic disease. This case highlights the aggressive biology of platinum-resistant primary mediastinal yolk sac tumors, illustrates primary resistance to programmed death-1 inhibition, and underscores the urgent need for more effective salvage strategies in this high-risk population.
2026-05-28 | Expression of nectin-4 in germ-cell tumors.
e17009 Background: Nectin-4 is a cell adhesion molecule and therapeutic target in several malignancies, including urothelial carcinoma. However, its expression pattern in germ cell tumors (GCT) remains poorly characterized. Given the limited treatment options for refractory GCTs, and the urgent need for novel therapeutic options, we present a retrospective analysis of Nectin-4 expression on pathology samples from patients with GCT. Methods: Samples from 93 unique patients with GCT from Indiana University Simon Comprehensive Cancer Center from 2010-2022 were identified. Patients with both seminoma and non-seminoma were included. Nectin-4 staining was performed by IQVIA Laboratories using the non-commercially available anti-Nectin-4 antibody (clone M22-312B41.1). Results: Overall, 93 samples were identified, 5 subjects did not have sufficient tissue to complete Nectin 4 testing. Of 88 evaluable samples, 43 (48.8%) demonstrated Nectin-4 expression. Expression varied significantly by histology. Teratoma demonstrated the highest prevalence, with 33 of 38 cases (86.8%) positive, with frequent high levels of expression (17 of 33 exhibiting ≥20% neoplastic cell positivity). Seminoma showed infrequent expression (3 of 29, 10.3%). No expression was observed in pure embryonal carcinoma (0 of 8). Yolk sac tumors demonstrated variable expression (3 of 7, 42.8%). Mixed histology tumors showed expression in 66% (4 of 6). Nectin-4 positivity was observed across multiple anatomic sites, including retroperitoneal lymph nodes (RP LN), lung, mediastinum, kidney, ureter, and other lymph nodes (LN) and metastatic locations. Conclusions: Nectin-4 varies across histology in GCT. Teratoma has the highest expression of Nectin-4 while embryonal carcinoma appears to have the lowest expression. Expression was not site restricted. These findings suggest that Nectin-4 may represent a biologically relevant therapeutic target especially in patients with unresectable teratoma. Nectin-4 expression by histologic subtype and anatomic site in germ cell tumors. Histology Nectin 4 expression (%) Sites All 43/88 (48.8%) Teratoma 33/38 (86.8%) RP LN (22)Lung (5)Mediastinum (3)Neck (1)Pelvic LN (1)Kidney (1) Seminoma 3/29 (10.3%) RP LN (2)Testis (1) Yolk Sac 3/7 (42.8%) RP LN (1)Ureter (1)Mediastinum (1) Embryonal Carcinoma 0/8 (0%) N/A Mixed Histology 4/6 (66.6%) Testis (1)RP LN (1)Mediastinum (2)
2026-05-22 | A Spotlight on Yolk-sac Tumors: Molecular Pathology, Current Diagnostics, and Novel Therapeutics.
Yolk-sac tumors are an aggressive subtype of testicular cancer that significantly contribute to disease progression and therapy resistance, especially in adults. While testicular cancer generally has high cure rates with cisplatin-based treatment, adult yolk-sac tumors often appear as components of mixed tumors with poor response to therapy and worse outcomes. Pediatric yolk-sac tumors tend to be pure and curable, but adult forms are biologically distinct and more aggressive. This review addresses the urgent clinical challenge posed by this disease by summarizing their pathophysiology, diagnostic biomarkers, and molecular drivers that sustain their aggressive behavior. By emphasizing key epigenetic and genetic alterations, as well as differentiation programs, this work highlights current and emerging therapeutic strategies aimed at improving early detection and treatment responses. Understanding yolk-sac tumor biology is essential to overcoming resistance and improving survival in patients affected by this high-risk tumor subtype.
2026-04-03 | Abstract 7220: Claudin-6 (CLDN6) expression is abundant in many different cancer entities
Abstract Claudin-6 (CLDN6) is a member of the claudin membrane protein family, which are crucial components of tight junctions, regulating paracellular permeability and maintaining cell polarity. CLDN6 is early expressed in embryonic stem cells and in specific fetal tissues such as kidney, lung, pancreas, and stomach, but is not expressed in corresponding adult tissues. While CLDN6 expression is largely lacking on normal tissues, it is highly expressed in several cancers. Therefore, CLDN6 is considered a potential therapeutic target. Studies evaluating CLDN6 as a target for monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, and CAR-T cells are underway. To better comprehend the prevalence of CLDN6 expression in different cancer types, CLDN6 was analyzed by immunohistochemistry (IHC) on tissue microarrays (TMAs) containing 4,464 samples from 101 different tumor types. A total of 39 tumor categories showed CLDN6 expression in at least one case, and 21 tumor categories contained at least one strongly positive case. At least weak CLDN6 positivity was most commonly seen in embryonal carcinoma (100%), seminoma (97.8%), and yolk sac tumor of the testis (97.6%), serous high-grade (76.4%), endometrioid (41.0%) and clear cell carcinoma (31.6%) of the ovary, carcinosarcoma of the ovary (66.7%) and the endometrium (36.0%), basal cell carcinoma of the skin (44.4%), adenocarcinoma of the ampulla Vateri (20%), endometrioid endometrial carcinoma (18.9%), adenocarcinoma of the cervix uteri (17.4%), adenocarcinoma of the esophagus (13.9%), gastric adenocarcinoma, intestinal type (11.6%), mucinous carcinoma of the ovary (9.1%), ductal adenocarcinoma of the pancreas (8.9%), muscle-invasive urothelial carcinoma (6.9%), cholangiocarcinoma (5.9%), squamous cell carcinomas of the esophagus (4.5%), vulva (4.3%), skin (4.1%), larynx (3.1%), penis (2.8%), pharynx (2.3%), anal canal (1.7%), oral cavity (1.2%), and the cervix uteri (1.2%), Brenner tumor of the ovary (3.6%), invasive breast carcinoma of no special type (3.5%), hepatocellular carcinoma (2.0%), gastric adenocarcinoma, diffuse type (1.8%), colorectal adenocarcinoma (1.7%), and diffuse large B cell lymphoma (1.0%). Our tumor cohorts were large enough to compare CLDN6 expression with tumor phenotype in ovarian, endometrial and pancreatic cancer. CLDN6 positivity was associated with advanced pT stage (p<0.0001) and high grade (p=0.0003) in ovarian cancer and with high grade in endometrial carcinoma (p=0.0179) but was unrelated to phenotype in pancreatic ductal adenocarcinoma. It is concluded that CLDN6 is expressed at significant levels in many different tumor types. Once anti-CLDN6 drugs are approved as safe and efficient, patients with many different cancer types may benefit from these new therapies. Citation Format: Veit Bertram, Anin Sharifi, Katharina Möller, Florian Lutz, Florian Viehweger, Christina Tsourlakis, Georgia Makrypidi-Fraune, Martina Kluth, Christian Bernreuther, Guido Sauter, Andreas H. Marx, Ronald Simon, Fiete Gehrisch, Nina Schraps, Stefan Steurer, Christoph Fraune, Viktoria Chirico, Clara von Bargen, Cosima Völkel, Morton Freytag, Natalia Gorbokon, Maximilian Lennartz, Eike C. Burandt, Anne Menz, Till Krech, Sarah Minner. Claudin-6 (CLDN6) expression is abundant in many different cancer entities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7220.
2025-11-14 | Partial Response to Sintilimab-Based Multimodal Therapy in a Refractory Primary Mediastinal Yolk Sac Tumor: A Case Report.
Primary mediastinal yolk sac tumor (PMYST) represents an extremely rare and highly aggressive germ cell malignancy with poor prognosis and limited therapeutic options. We report a 55-year-old male who presented with a large anterior mediastinal mass measuring 149 × 73 mm and significantly elevated serum alpha-fetoprotein (AFP) levels (>1210 ng/mL). Histopathological examination and immunohistochemical staining confirmed the diagnosis of PMYST. An interim response was observed after one cycle of etoposide-cisplatin chemotherapy given concurrently with radiotherapy. However, upon completion of the entire chemoradiotherapy course (radiotherapy plus three cycles of chemotherapy), the patient was found to have disease progression with an enlarging tumor burden. Subsequently, sintilimab-based chemo-immunotherapy was initiated, resulting in a partial response achieved after four cycles of treatment. At the most recent follow-up, the patient demonstrates sustained clinical stability with continued disease control. This case highlights the potential efficacy of PD-1 inhibitor-based combination therapy in refractory mediastinal yolk sac tumor (YST), which may provide a novel therapeutic strategy for managing this challenging malignancy.
cell therapies
2026-01-05 | Establishment of a Patient-Derived Xenograft Model of a Testicular Yolk Sac Tumor.
We have established a highly stable and reproducible patient derived xenograft model that exclusively and robustly retains the morphological, functional, and proliferative characteristics of human yolk sac tumor of the testis. This model might provide an invaluable in vivo platform for accelerating the discovery and validation of novel therapeutic strategies for this aggressive malignancy, with the ultimate aim of improving the prognosis for affected patients.
2025-05-10 | Human malignant ovarian germ cell tumor cell lines derived from peritoneal cytology retrieving from circulating tumor cell system.
Malignant ovarian germ cell tumor (MOGCT) is a rare neoplasm predominantly affecting adolescent and young adult females. Establishing personalized permanent tumor cell lines is crucial for understanding tumor behavior and optimizing precision treatment for these patients. We developed a novel procedure for isolating and culturing human MOGCT cells from peritoneal wash cytology using the circulating cell extraction technique (Labyrinthbiotech Co. LLC, LABYRINTHCE01, China). Peripheral blood and peritoneal washings were collected from 15 patients, including those with yolk sac tumor (n = 6), dysgerminoma (n = 2), immature teratoma (n = 5), and mixed germ cell tumor (n = 2). After washing and centrifugation, samples were processed using the labyrinth technique to achieve high-purity cell cultures. The isolated tumor cells were characterized by immunofluorescence microscopy and flow cytometry. Immunohistochemical analysis enabled specific discrimination from primary peritoneal human fibroblasts. Cultures were established from peritoneal cytology with cell densities ranging from 10² to 10⁵ cells per well, with 5 samples showing over 10⁵ cell growth, 3 samples over 10⁴ cell growth, and others at 10³ cell growth. The longest cell culture has been maintained for 18 generations. Short tandem repeat (STR) analysis of cultured cells confirmed their germ cell tumor origin. Preliminary assessments of chemosensitivity in cultured cells have been found to reflect similar clinical responses in the corresponding patients. The MOGCT cell lines derived from peritoneal washings using the circulating tumor cell chip represent the tumor characteristics. This method holds promise for functional studies on rare ovarian tumors and for evaluating chemo-sensitivity for potential therapeutic applications.
2023-02-13 | Immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR)-T cell therapy: Potential treatment options against Testicular Germ Cell Tumors
Germ cell tumors (GCTs) represent a heterogeneous neoplasm family affecting gonads and rarely occurring in extragonadal areas. Most of patients have a good prognosis, often even in the presence of metastatic disease; however, in almost 15% of cases, tumor relapse and platinum resistance are the main challenges. Thus, novel treatment strategies with both improved antineoplastic activity and minor treatment-related adverse events compared with platinum are really expected. In this context, the development and the high activity demonstrated by immune checkpoint inhibitors in solid tumors and, subsequently, the interesting results obtained from the use of chimeric antigen receptor (CAR-) T cell therapy in hematological tumors, have stimulated research in this direction also in GCTs. In this article, we will analyze the molecular mechanisms underlying the immune action in the development of GCTs, and we will report the data from the studies that tested the new immunotherapeutic approaches in these neoplasms.
2020-03-19 | Establishment and Characterization of a Novel Primitive Yolk Sac Tumour Cell Line, TC587.
Yolk sac tumour (YST) is a rare malignant ovarian germ cell tumour that often occurs in young women or adolescents and exhibits an unfavourable outcome. To evaluate the biological behavior of carcinomas in vitro, permanent tumour cell lines are required. However, previously, only a few human YST cell lines have been established. Therefore, we aimed to establish a novel YST cell line. We established a novel YST cell line, TC587, from an adolescent patient with ovarian YST. The cell line expressed AFP and SALL4, the characteristics of YST. In addition, we evaluated somatic mutations using next-generation sequencing and revealed some pathogenic variants, including mutations in the NRAS, KIT, KMT2C, RSF1, and TP53 genes. The newly established TC587 cell line may represent an effective tool for developing treatments and conducting molecular analyses for YST.
2019-12-18 | Salvage treatment for children with relapsed/refractory germ cell tumors: The Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) experience
Abstract Background Malignant germ cell tumors (GCTs) are a heterogeneous group of rare neoplasms in children. Optimal outcome is achieved with multimodal therapies for patients with both localized and advanced disease, especially after the introduction of platinum‐based chemotherapy regimens. In this respect, data on salvage treatment for children with relapsed or platinum‐refractory disease are still limited. Methods Retrospective analysis of data regarding patients affected by malignant GCTs with platinum‐refractory or relapsed disease after first‐line treatment according to AIEOP TCGM 2004 protocol was conducted. Results Twenty‐one patients, 15 females and 6 males, were considered for the analysis. All 21 patients received second‐line conventional chemotherapy (SLCT), two of these immediately after surgery for local relapse removal. Two patients showed a progression of disease during SLCT and died of disease shortly thereafter, whereas 19 patients were in partial remission (PR) or complete remission (CR) after SLCT. Treatment after SLCT consisted in surgery on residual tumor mass (9/19) followed by high dose of chemotherapy (HDCT) with autologous hematopoietic stem cell support (16/19). The overall survival (OS) and event‐free survival of the whole populations are 71% and 66.6%, respectively. Platinum‐refractory patients OS is 54.5% compared with 91.5% of the relapsed group. There were no treatment‐related deaths. Conclusion SLCT followed or not by HDCT is an effective salvage treatment for children with relapsed/refractory GCTs. However, the role of HDCT following SLCT needs to be further investigated, especially regarding the identification of specific patient subgroups, which can benefit from this more intensive treatment.
oligonucleotides
2023-11-27 | Testicular germ cell tumour cells release microRNA-containing extracellular vesicles that induce phenotypic and genotypic changes in cells of the tumour microenvironment.
Malignant germ-cell-tumours (GCTs) are characterised by microRNA (miRNA/miR-) dysregulation, with universal over-expression of miR-371~373 and miR-302/367 clusters regardless of patient age, tumour site, or subtype (seminoma/yolk-sac-tumour/embryonal carcinoma). These miRNAs are released into the bloodstream, presumed within extracellular-vesicles (EVs) and represent promising biomarkers. Here, we comprehensively examined the role of EVs, and their miRNA cargo, on (fibroblast/endothelial/macrophage) cells representative of the testicular GCT (TGCT) tumour microenvironment (TME). Small RNA next-generation-sequencing was performed on 34 samples, comprising representative malignant GCT cell lines/EVs and controls (testis fibroblast [Hs1.Tes] cell-line/EVs and testis/ovary samples). TME cells received TGCT co-culture, TGCT-derived EVs, and a miRNA overexpression system (miR-371a-OE) to assess functional relevance. TGCT cells secreted EVs into culture media. MiR-371~373 and miR-302/367 cluster miRNAs were overexpressed in all TGCT cells/subtypes compared with control cells and were highly abundant in TGCT-derived EVs, with miR-371a-3p/miR-371a-5p the most abundant. TGCT co-culture resulted in increased levels of miRNAs from the miR-371~373 and miR-302/367 clusters in TME (fibroblast) cells. Next, fluorescent labelling demonstrated TGCT-derived EVs were internalised by all TME (fibroblast/endothelial/macrophage) cells. TME (fibroblast/endothelial) cell treatment with EVs derived from different TGCT subtypes resulted in increased miR-371~373 and miR-302/367 miRNA levels, and other generic (eg, miR-205-5p/miR-148-3p) and subtype-specific (seminoma, eg, miR-203a-3p; yolk-sac-tumour, eg, miR-375-3p) miRNAs. MiR-371a-OE in TME cells resulted in increased collagen contraction (fibroblasts) and angiogenesis (endothelial cells), via direct mRNA downregulation and alteration of relevant pathways. TGCT cells communicate with nontumour stromal TME cells through release of EVs enriched in oncogenic miRNAs, potentially contributing to tumour progression.
2023-11-08 | Targeting oncogenic microRNAs from the miR-371~373 and miR-302/367 clusters in malignant germ cell tumours causes growth inhibition through cell cycle disruption.
MiR-371~373 and miR-302/367 cluster over-expression occurs in all malignant germ cell tumours (GCTs), regardless of age (paediatric/adult), site (gonadal/extragonadal), or subtype [seminoma, yolk sac tumour (YST), embryonal carcinoma (EC)]. Six of eight microRNAs from these clusters contain the seed sequence 'AAGUGC', determining mRNA targeting. Here we sought to identify the significance of these observations by targeting these microRNAs functionally. We targeted miR-371~373 and/or miR-302/367 clusters in malignant GCT cell lines, using CRISPR-Cas9, gapmer primary miR-302/367 transcript inhibition, and peptide nucleic acid (PNA) or locked nucleic acid (LNA)-DNA inhibition targeting miR-302a-d-3p, and undertook relevant functional assays. MiR-302/367 cluster microRNAs made the largest contribution to AAGUGC seed abundance in malignant GCT cells, regardless of subtype (seminoma/YST/EC). Following the unsuccessful use of CRISPR-Cas9, gapmer, and PNA systems, LNA-DNA-based targeting resulted in growth inhibition in seminoma and YST cells. This was associated with the de-repression of multiple mRNAs targeted by AAGUGC seed-containing microRNAs, with pathway analysis confirming predominant disruption of Rho-GTPase signalling, vesicle organisation/transport, and cell cycle regulation, findings corroborated in clinical samples. Further LNA-DNA inhibitor studies confirmed direct cell cycle effects, with an increase of cells in G0/G1-phase and a decrease in S-phase. Targeting of specific miR-371~373 and miR-302/367 microRNAs in malignant GCTs demonstrated their functional significance, with growth inhibition mediated through cell cycle disruption.
2023-03-30 | Supplementary Figures 1-12 from <i>LIN28</i> Expression in Malignant Germ Cell Tumors Downregulates <i>let-7</i> and Increases Oncogene Levels
<p>PDF - 492K, Supplementary Figure 1: Levels of the nine members of the let-7 family in pediatric malignant-GCTs. Supplementary Figure 2: PCR quantification of let-7e, LIN28 and LIN28B in malignant-GCTs.Supplementary Figure 3: Sylamer analysis of up-regulated genes in pediatric and adult malignant-GCTs. Supplementary Figure 4: Correlations between levels of let-7 and mRNA targets. Supplementary Figure 5: PCR quantification of HMGA2 in pediatric malignant-GCTs. Supplementary Figure 6: PCR validation of expression of selected let-7 mRNA targets in pediatric malignant-GCTs. Supplementary Figure 7: Effects of LIN28 depletion in malignant-GCT cells. Supplementary Figure 8: Independent confirmation of specific effects of LIN28 depletion in malignant-GCT cells. Supplementary Figure 9: Effects of let-7e mimic in malignant-GCT cells. Supplementary Figure 10: Relationships between MYCN and C-MYC versus LIN28 and LIN28B in malignant-GCTs. Supplementary Figure 11: MYCN depletion in malignant-GCTs (S11). Supplementary Figure 12: Schematic of the LIN28/let-7 axis in malignant-GCTs.</p>
2023-02-16 | Silencing of LINC00467 inhibits cell proliferation in testicular germ cell tumors cells Running Title: Silencing of LINC00467 regulates cell proliferation
Abstract Our previous study showed that LINC00467 expression decreased significantly in testicular germ cell tumors (TGCTs) compared with adjacent tissue. LINC00467 expression in TGCTs was upregulated at stages II/III compared with stage I, and was negatively correlated with the 5-year overall survival and 5-year disease-free survival. However, the role of LINC00467 in the development of TGCTs remains to be elucidated further. LINC00467 expression was silenced in the NCCIT and TCAM-2 cell lines using small interfering RNA (siRNA). The expression level of genes was validated using quantitative real-time polymerase chain reaction (qRT-PCR) analyses. The MTT and CCK8 assays were used to detect cell proliferation. The effects on cell cycle were evaluated using flow cytometry. Western blotting analysis was used to detect the expression level of proteins, while RNA-sequencing and bioinformatics methods were used to explore the mechanism of action of LINC00467 in TGCTs. The silencing of LINC00467 expression decreased cell proliferation, induced S phase arrest, and downregulated the cell cycle-related protein PCNA expression while upregulating the expression of P21. Dihydrotestosterone (DHT) stimulation experiments showed that DHT could upregulate the expression of LINC00467 and that the silencing of LINC00467 could reverse the effect of testosterone on cell proliferation. The Gene Set Enrichment Analysis (GSEA) showed that the P53 signaling pathway was associated with LINC00467. Our study reported that LINC00467 regulated cell proliferation and induced S phase arrest in TGCTs cells through the cell cycle-related proteins, PCNA, and P21. These enriched the mechanism of non-coding RNAs in the development of TGCTs.
2022-09-09 | Chromosome 3p25.3 Gain Is Associated With Cisplatin Resistance and Is an Independent Predictor of Poor Outcome in Male Malignant Germ Cell Tumors.
Cisplatin is the main systemic treatment modality for male type II germ cell tumors (GCTs). Although generally very effective, 5%-10% of patients suffer from cisplatin-resistant disease. Identification of the driving mechanisms of resistance will enable improved risk stratification and development of alternative treatments. We developed and characterized cisplatin-resistant GCT cell line models and compared their molecular characteristics with patient samples with cisplatin resistance and/or a poor clinical outcome. Subsequently, the association between the overlapping genetic features and clinical data was assessed. Finally, we used Cox regression to determine the prognostic relevance of these features within the currently used risk classification. Gain of chromosome 3p25.3 was detected in all cisplatin-resistant cell lines, and copy number of this region correlated with the level of resistance (R = 0.96, P = 1.5e-04). Gain of this region was detected at low frequencies in primary tumors and at higher frequencies in relapsed and/or cisplatin-resistant tumors. Chromosome 3p25.3 gain was associated with shorter progression-free survival and overall survival, with the strongest association observed in nonseminomas excluding pure teratomas. 3p25.3 gain was more frequently observed in tumors with yolk sac tumor histology and predicted adverse outcome independent of the International Germ Cell Cancer Collaborative Group risk classification and the presence of TP53/MDM2 alterations. On the basis of both in vitro analyses and clinical data, we found 3p25.3 to be strongly associated with cisplatin resistance and poor clinical outcome in male type II GCTs. Using genomic profiling, 3p25.3 status could help to improve risk stratification in male patients with type II GCT. Further characterization of this locus and underlying mechanisms of resistance is warranted to guide development of novel treatment approaches for cisplatin-resistant disease.
other
2026-09-18 | Intracardiac Metastasis From a Testicular Yolk Sac Tumor With Brain and Pulmonary Involvement: A Multimodality Management Case Report.
Cardiac metastasis from non-seminomatous germ cell tumors (NSGCTs) is exceedingly rare and represents an aggressive disease course. We report a 37-year-old man with a testicular yolk sac tumor who initially declined adjuvant therapy after orchiectomy. He later developed pulmonary metastases treated with BEP chemotherapy, followed by progressive disease with brain involvement requiring emergent decompressive craniectomy and whole-brain radiotherapy. Salvage TIP chemotherapy was administered. Persistent pulmonary disease led to thoracotomy, during which a discrete metastatic deposit in the right atrium was identified and surgically resected. Histopathology confirmed metastatic yolk sac tumor in all sites. The patient subsequently received maintenance therapy with oxaliplatin and bevacizumab. Follow-up has been based on clinical assessment and serial tumor marker monitoring, demonstrating ongoing biochemical and clinical stability for approximately 6 months following initiation of maintenance therapy, with the patient remaining on treatment at the time of this report. This case highlights the unpredictable metastatic behavior of NSGCTs and underscores the importance of multidisciplinary management in achieving disease control in rare and life-threatening metastatic presentations.
2024-03-11 | An unusual association of deletion of SMARCB1 in a patient with intracranial yolk sac tumor: A case-report
Deletion of SMARCB1/loss of INI is a well-known association in atypical rhabdoid teratoid tumors (ATRT) in the brain, rhabdoid tumors in the kidney, and less common tumors systemic tumors like sinonasal INI1 deficient carcinoma, gastric undifferentiated carcinoma, undifferentiated uterine sarcomas, and poorly differentiated chordomas. We describe homozygous deletion of the SMARCB1 gene in a patient diagnosed with pineal yolk sac tumor (YST), which is a rare entity. This association highlights the importance of INI1 staining when the clinical course is not progressing as expected and brings us to a critical management question: should this rare entity be treated more aggressively, like ATRT, versus the conventional approach to intracranial YST?
2024-02-27 | Overexpression of SerpinB9 in non-seminomatous germ cell tumors.
Serpinb9 is an inhibitor of granzyme B and is potentially involved in the immune escape of tumor cells. In the present study, bioinformatics analysis using open databases suggested that SerpinB9 is overexpressed in testicular embryonal carcinoma. Immunohistological analysis was performed on 28 cases of testicular germ cell tumors to investigate the relationship between SerpinB9 expression in testicular germ cell tumors and the tumor immune environment. SerpinB9 was significantly upregulated in the non-seminoma group and inversely correlated with the number of tumor-infiltrating CD8-positive cells. In addition, yolk sac tumors were characterized by the loss of human leukocyte antigen-class I expression. These findings suggest that SerpinB9 contributes to the immune escape of testicular germ cell tumors. Targeting therapy for SerpinB9 might therefore be useful in immunotherapy for testicular germ cell tumors resistant to immune checkpoint inhibitors.
2023-12-19 | Administration of a glypican-3 peptide increases the infiltration and cytotoxicity of CD8+ T cells against testicular yolk sac tumor, associated with enhancing the intratumoral cGAS/STING signaling.
Glypican-3 (GPC3) is highly expressed in testicular yolk sac tumor (TYST). GPC3 has been evaluated as a cancer vaccine for some types of tumors, but little is known on the effects of GPC3 peptide-based therapy on TYST. Here, we evaluated the antitumor effect of GPC3144-152 on TYST and its potential mechanisms. GPC3144-152 -specific CD8+ T cells were induced by vaccine immunization and examined by ELISPOT. The CD8+ T cells were purified for testing their cytotoxicity in vitro against TYST cells by CCK-8 and TUNEL assays and in vivo against tumor growth. The influence of GPC3144-152 loading and/or cGAS silencing on the tumor growth, apoptosis and cGAS/STING signaling was tested by immunohistochemistry, immunofluorescence, flow cytometry, and Western blot. Vaccination with GPC3144-152 induced tumor-specific CD8+ T cells that secreted high levels of IFN-γ and granzyme B, and had potent cytotoxicity against TYST in a dose-dependent manner. Adoptive transfer of CD8+ T cells and treatment with GPC3144-152 significantly inhibited the growth of TYST tumors, but less effective for cGAS-silenced TYST tumors in vivo. Treatment with GPC3144-152 enhanced the infiltration of CD8+ T cells into the tumor environment and their cytotoxicity against TYST tumors in vivo by up-regulating granzyme B and IFN-β expression, but down-regulating GPC3 expression in the tumors. Co-culture of CD8+ T cells with TYST in the presence of exogenous GPC3144-152 enhanced peptide-specific CD8+ T-cell cytotoxicity in vitro, accompanied by enhancing cGAS, γH2AX, TBK1, and IRF3 phosphorylation in TYST cells, but less effective in cGAS-silenced TYST cells. These data indicated that GPC3 peptide-specific CD8+ T cells had potent antitumor activity against TYST tumor, particularly for combined treatment with the peptide, which was partially dependent on the intratumoral cGAS/STNG signaling. GPC3 peptide vaccine may be valuable for the combination treatment of TYST.
2021-10-22 | Preservation of Fertility in a Patient with a Mixed Germ Tumor and Subsequent Successful Pregnancies. A Case Report
Objective:The objective of the study was to present the case of a patient with a diagnosis of a mixed germ cell tumor clinical stage (CS) IIC, who underwent conservative cytoreductive surgery and chemotherapy before initiation of a gonadotropin-releasing hormone agonist (GnRH-a) for fertility preservation, subsequently achieving spontaneous pregnancies.Material and methods: A 19-year-old patient underwent an examination for abdominal distention.Through clinical and imaging studies, an abdominal-pelvic mass of 15 cm × 14 cm × 10 cm was diagnosed with a location in the right ovary.After optimal cytoreductive surgery, the report confirmed a conservative germinal mixed tumor histopathology (80% endodermic sinuses and 20% embryonal carcinoma), CS IIC, so 4 cycles of chemotherapy were indicated.Before the start of and throughout the cytotoxic treatment, GnRH-a was administered.Results: At the end of the oncological treatment, a follicle stimulating hormone of 20 mUI/mL was reported, spontaneous resumption of menstrual cycles was presented 2 months after having concluded chemotherapy and suspended the use of GnRH-a.12 months later, a spontaneous pregnancy was normally achieved, which ended with a live newborn at 38.4 weeks of gestation, and 4 years later, a second spontaneous pregnancy, which also culminated in obtaining a healthy newborn.Conclusions: Fertility preservation should be considered a fundamental aspect of the quality of life of cancer survivors.Provided that there are no contraindications, the use of GnRH-a should be considered before the start of chemotherapy, remembering that this treatment could offer benefits beyond the preservation of fertility (bone, sexual, and cardiovascular health), providing comprehensive management.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
1 orphan drug designation for Yolk sac tumor.
1 orphan drug designation for Yolk sac tumor.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Technetium Tc99m murine monoclonal antibody to human AFP | antibodies | FDA | — | Immunomedics, Inc. |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI’s forecasts to outperform average preclinical success rates. Whether you’re expanding your R&D pipeline, evaluating a partnership, or simply have a question — we’d love to hear from you.