Germ Cell Tumors

Though promising, miRNAs are limited by their inability to detect teratoma. ctDNA and CTCs are two other emerging biomarkers, though further studies are needed to clarify their role in managing patients with GCT.

ROC curve analysis confirmed that miR-126 upregulation is able to identify cancer patients among the infertile male population. In addition, in-depth bioinformatics analysis based on weighted gene co-expression networks showed that the identified miRNAs regulate cellular pathways involved in cancer.

In summary, these data show that PLAP is expressed in a significant fraction of pT2-4 urothelial carcinomas, unrelated to cancer aggressiveness but associated with specific molecular features. Once anti-PLAP cancer drugs become effective, urothelial carcinoma is a candidate tumor entity for clinical evaluation.

However, few responses to PARPis in TGCTs have been detected in patients with BRCA1/2, ATM or CHEK2 mutations, reinforcing the idea that patients should be optimally selected for tailored treatments in the era of personalized medicine. Future preclinical and clinical research is needed to further investigate the molecular mechanisms of cisplatin resistance and to identify novel therapeutic strategies in resistant/refractory TGCTs patients.

Treatment for the PNET included vincristine, doxorubicin, cyclophosphamide, and ifosfamide/etoposide mesna...The patient also underwent a tandem autologous stem cell transplant with carboplatin/etoposide conditioning and adjuvant etoposide and the subsequent PET/CT scan showed a response to the above treatment...The regimen for our patient yielded promising results. Our aim is to highlight a regimen that can be utilized for this rare aggressive neoplasm.

P1, N=11, Completed, Seattle Children's Hospital | Active, not recruiting --> Completed | Trial completion date: Mar 2040 --> Dec 2023 | Trial primary completion date: Mar 2025 --> Dec 2023

P1, N=10, Active, not recruiting, Seattle Children's Hospital | Trial primary completion date: Jul 2024 --> Jul 2025

P1/2, N=126, Recruiting, Cancer Trials Ireland | Active, not recruiting --> Recruiting

This spatial expression pattern of SOX2 and FOXG1 proteins observed in immature teratoma mirrors the lineage differentiation and migration trajectories of primitive neuroepithelial components typically seen in embryonic neurogenesis and cortical development. In daily practice, the combined application of SOX2 and FOXG1 SOX2 and FOXG1 helps identify the primitive neuroepithelial components in immature teratoma, avoid misjudgment of similar morphologies, and thereby assist in the histological grading and clinical decision-making.

Our findings suggest the involvement of the CacyBP/SIP protein in the ERK1/2 and p38 signalling pathways, which may be involved in the processes of testicular seminoma carcinogenesis. The results of our research provide the basis for further research in this area.

P2, N=240, Recruiting, Children's Oncology Group | Initiation date: Jun 2025 --> Oct 2024

Frequent findings were FIGO stage II, cytoreductive surgery, immunohistochemical analyses of a large panel of markers, postoperative chemotherapy, and no tumor recurrence (except in 1 patient who died), although the length of follow-up was relatively short or unclearly stated. The present case report illustrates that yolk sac tumors in very old women may have a favorable clinical course without signs of recurrence even in the absence of radical surgical resection with curative intent and associated adjuvant chemotherapy.

P2, N=30, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

P3, N=246, Completed, Institute of Cancer Research, United Kingdom | Unknown status --> Completed | Trial completion date: Aug 2020 --> Sep 2024

In vivo experiments exhibited that AMH-4 was more effective than lartesertib and vorinostat in inhibiting the growth of NTERA-2 cL.D1 xenograft tumors with low toxicity. Overall, these results suggest that AMH-4 is an effective and low toxicity candidate for the treatment of testicular germ cell tumors.

MicroRNA-371a-3p is a promising, highly sensitive marker for TGCTs, offering better performance and cost efficiency than conventional STMs, likely to become the next-generation diagnostic tool for TGCTs.

Postoperatively, he received adjuvant chemotherapy with 2 cycles of a cisplatin based regimen for clinical stage 1 disease...Conclusion Histogenetically, testicular germ cell tumours are thought to derive from the precursor germ cell neoplasia in situ while spermatocytic tumours directly derive from adult spermatogonia. This case is exceptional, firstly because of the very long interval of 27 years between the two neoplastic events, and secondly, because of the unprecedented occurrence of two testicular neoplasms with different pathogenetic origins in one individual patient.

P2, N=262, Completed, Children's Oncology Group | Active, not recruiting --> Completed

LINC00470 may play a significant role in the etiology and metastasis of TGCT through EMT and AKT-mediated signaling pathways.

Cells were treated with demethylating 5-azacytidine and pyrosequencing was performed...In summary, combination miR-100-5p/miR-125b-5p mimic replenishment or TRIM71kd caused growth inhibition in malignant GCT cells via cell cycle disruption. Further studies are now warranted, including mimic treatment alongside conventional platinum-based chemotherapy.

Our research indicates that SERPINB9 plays a key role in driving tumor progression by enhancing tumor stemness and suppressing TLS. This study stands as the first to elucidate the molecular signature of non-seminomas at a single-cell level, presenting a wealth of promising targets with substantial potential for informing the development of future therapeutic interventions.

P=N/A, N=0, Not yet recruiting, Sun Yat-sen University Cancer Center; Sun Yat-sen University Cancer Center

P=N/A, N=44, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

Additionally, pathway enrichment suggested that NUMB is involved in the Wnt pathway. This study highlights the predictive role of CTNNB1 across cancers, suggesting that CTNNB1 might serve as a potential biomarker for the diagnosis and prognosis evaluation of various malignant tumors.

P=N/A, N=1275, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

We sought to evaluate the genomic and transcriptomic landscapes in primary and metastatic germ cell tumors (GCTs; N = 138) to uncover factors that drive cisplatin resistance...PRA-positive PreC GCTs had significantly lower average PSS scores compared to PRA-negative tumors. Lower PSS scores in chemo-naïve tumors were associated with PRAs, suggesting a potential mechanism for platinum resistance.

In this report, we demonstrate for the first time that targeting polycomb demethylases KDM6A and KDM6B with epidrug GSK-J4 can treat both cisplatin-sensitive and -resistant TGCTs. Further, several chromatin modifier genes, including BRD4 , lysine demethylases, chromodomain helicase DNA binding proteins, and lysine methyltransferases, were repressed with cisplatin only in KDM6A/KDM6B-targeted cells, implying that KDM6A/KDM6B inhibition sets the stage for extensive chromatin remodeling of TGCT cells upon cisplatin treatment. Our findings demonstrate that targeting polycomb demethylases is a new potent pharmacologic strategy for treating cisplatin resistant TGCTs that warrants clinical development.

The sacral approach for SCT excision was employed for the great majority of our patients, but due to the advanced age at diagnosis and locally advanced disease, morbidities occurred in about a third of the patients. Therefore, early detection prenatally and early referral to a pediatric surgical center should be achievable goals for physicians dealing with these patients.

While GSK-J4 had minimal effects alone on TGCT tumor growth in vivo, it dramatically sensitized cisplatin-sensitive and -resistant TGCTs to cisplatin...Further, several chromatin modifier genes, including BRD4, lysine demethylases, chromodomain helicase DNA binding proteins, and lysine methyltransferases, were repressed with cisplatin only in KDM6A/KDM6B-targeted cells, implying that KDM6A/KDM6B inhibition sets the stage for extensive chromatin remodeling of TGCT cells upon cisplatin treatment. Our findings demonstrate that targeting polycomb demethylases is a new potent pharmacologic strategy for treating cisplatin resistant TGCTs that warrants clinical development.

The International Mesothelioma Interest Group recommends using at least 2 mesothelial markers, such as calretinin, WT1, CK5/6 or D2-40, and 2 epithelial markers, such as claudin-4, CEA, MOC-31, as well as a broad-spectrum cytokeratin stain (AE1/AE3) as part of an initial immunohistochemical panel. Metastatic mesothelioma should be included in the differential diagnosis of malignant epithelioid dermal tumors with unusual staining patterns.

P2, N=23, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed

The involvement of TILs in seminoma biology warrants further investigation, especially their role in the tumor micro-environment and pathogenesis. Chemokine and Ki-67 expression in TILs could serve as potential markers for assessing seminoma prognosis.

P=N/A, N=400, Recruiting, Eastern Cooperative Oncology Group | Trial completion date: Nov 2024 --> May 2027 | Trial primary completion date: Nov 2024 --> May 2027

This is the first report of a patient with heterochronous double primary tumor of BGGCT followed by DHGs.

Despite surgery and chemotherapy, two patients died of disease 17 months after ETT diagnosis, and three patients were alive with metastatic disease at a mean of 20 months (range, 15-28 months). Our results demonstrate that ETT may be an aggressive disease associated with distinct pathologic features and poor clinical outcome.

Thus, our data indicate a possible function of TAF7 in the regulation of SSCs and spermatogenesis following downregulation by Busulfan. These findings may account for the therapeutic effects of Busulfan and underlie its potential impact on cancer chemotherapy prognosis.

Research is also currently being conducted on circulating tumor cells (CTCs) and cell-free DNA (cfNA) in various areas of application. With regard to germ cell tumors of the testis, however, these analyses are still in their infancy, but it is hoped that this will provide a further sufficient opportunity to use serum tumor markers.

P2, N=4, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Sep 2025

Management of SCYSTs is complex and requires a multidisciplinary approach, including surgeons, oncologists, radiologists, and pathologists. While relapse is rare, it poses a significant challenge for treatment, underscoring the need for clear and updated guidelines for managing relapsed cases.

P1, N=245, Recruiting, Incyte Corporation | N=165 --> 245

Finally, the proliferation, migration, and invasion of NT2/D1 cells simulated by E2 or ESR2 were also blocked by PP2 and U0126. This study provides novel insights into molecular mechanisms of ER in NT2/D1 cells by demonstrating that ER activates rapid responses molecules, including SRC and ERK1/2, which enhance the tumorigenic potential of testicular cancer cells.

In addition, compared with PD-L1-negative yolk sac tissue, dysgerminomas/seminomas with high PD-L1 expression are associated with more genetic alterations and a better prognosis. Our findings will contribute to the knowledge about the potential benefits of ovarian cancer immunotherapy in specific subsets of germ cell tumor patients and the risk factors for resistance mediated by tumor microenvironment cells.