Emerging Therapeutic Targets for Male Germ Cell Tumors

Abstract

Male germ cell tumors (GCTs) are curable cancers, yet 10-15 % of patients with metastatic disease fail cisplatin-based first-line treatments. While therapeutic options have increased for various other cancers, little progress has been made in the management of GCT in the last decades. A better understanding of the molecular alterations underlying the disease and identification of new therapeutic targets are needed. Several phase I/II studies with promising new agents are ongoing or have been completed, but most of those trials have been small and have not included translational research. Therefore, molecular profiles predictive for response or new agents have not been identified in male GCT so far. The purpose of this review is to highlight emerging targets and therapies with the potential to improve systemic treatment of metastatic male GCT and to develop strategies for future clinical trials.

Identification of programmed cell death 1 and its ligand in the testicular tissue of mice

“…However, spermatocytes and spermatids were the main cell types that expressed PD-L1 in the seminiferous tubules in an allograft study. 32 In addition, recent data showed that there was little or no PD-L1 expression, 33,34 and PD-1 expression was also not detected in normal human testes. 34 This ambiguity surrounding expression made it difficult to identify the exact function of the PD-1/PD-L1 pathway in testicular functions.…”

“…32 However, controversial results were obtained in human testes. Based on immunohistochemical staining, researchers claimed that there was no 33 Complete spermatogenesis is established in the testes of adult mice.…”

“…vival of intra-testicular allografts, and spermatocytes and spermatids were mainly PD-L1 + cells in the seminiferous tubules of the testes based on immunohistochemical staining 32. Based on immunohistochemical staining, researchers claimed that there was no33 or little 34 PD-L1 expression in normal human testes. Based on immunohistochemical staining, researchers claimed that there was no33 or little 34 PD-L1 expression in normal human testes.…”

Pediatric Extracranial Germ Cell Tumors: Review of Clinics and Perspectives in Application of Autologous Stem Cell Transplantation

“…The associated toxicity should be taken into consideration [ 64 ]. Frankhauser et al found that the expression of PD-1 and PDL-1 were high in GCTs which may bring insight to immune checkpoint inhibitor treatment [ 65 ]. A previous report suggested that a disseminated platinum refractory non-seminomatous GCTs showed response with tumor marker decline after initiating off-label nivolumab; however the patient had new brain metastasis 5 months later [ 66 ].…”

New Therapies Expanding treatment options and ongoing challenges for urologic cancers

“…In general, the common mutations in oncogenes and tumor suppressors that are observed in other tumor types are relatively rare in testicular cancers and among the potentially targetable genomic alterations that have been identi ed, such as mutations in the FGFR, AKT and PIK3CA genes, it is unclear what role these might play in the development of chemoresistance, if any. 28 Some progress is being made in certain types of testicular cancer and several di erent treatment strategies continue to be evaluated. Among those drugs that look promising in early-stage clinical testing are cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors.…”