RAS/Mitogen-Activated Protein Kinase Signaling Pathway in Testicular Germ Cell Tumors

Abstract

Germ cell tumors (GCTs) are relatively rare tumors. However, they are the most diagnosed malignancies occurring in the testis among men aged between 15 and 40 years. Despite high aneuploidy and a paucity of somatic mutations, several genomic and transcriptomic assays have identified a few significantly mutated somatic genes, primarily KIT and K-RAS. The receptor Tyrosine Kinase (RTK) pathway and the downstream related Mitogen-Activated Protein Kinase (MAPK) cascades are crucial signal transduction pathways that preside over various cellular processes, including proliferation, differentiation, apoptosis, and responses to stressors. They are well described in solid malignancies, where many of the involved factors are used as prognostic molecular markers or targets for precision therapy. This narrative review focused, in the first part, on PGCs’ survival/proliferation and differentiation and on the genetic and epigenetic factors involved in the pathogenesis of testicular germ cell tumors (TGCTs) and, in the second part, on the most recent investigations about the KIT-RAS pathway in TGCTs and in other cancers, highlighting the efforts that are being made to identify targetable markers for precision medicine approaches.

Recent Advancements in Research on DNA Methylation and Testicular Germ Cell Tumors: Unveiling the Intricate Relationship

“…Other cellular mechanisms, such as the RAS/MAPK signaling pathway, also play crucial roles in the development and progression of TGCTs. Recent studies, such as those by Onorato et al, highlight the significance of these pathways, which interact with epigenetic mechanisms, potentially influencing the methylation status of key genes involved in tumor behavior [69]. Understanding these interactions could offer new insights into comprehensive therapeutic targets beyond epigenetic modifications alone.…”