Novel biomarkers and emerging therapeutic strategies in testicular germ cell tumors

The diagnostic and treatment landscape for patients with Testicular Germ-Cell Tumors (TGCTs) is evolving. The discovery of two novel biomarkers, MicroRNA-371a-3p (miR-371) and circulating tumor DNA (ctDNA), have shown promise in initial studies and appear to offer superior sensitivity and specificity over conventional tumor markers. In patients with progressive disease after salvage and/or high-dose chemotherapy (HDCT), treatment options remain limited. While immune-checkpoint inhibition in this patient population has shown limited efficacy, several new therapeutic strategies have emerged with the most notable one being the targeting of Claudin-6 (CLDN6). Here, we will highlight recent advances with miR-371 and ctDNA, review their potential role in the initial diagnosis, minimal residual disease (MRD) assessment, and discuss their role as a prognostic biomarker. We will review the recent and ongoing efforts to improve survival outcomes in patients with refractory TGCTs including immune-checkpoint and CD30 inhibition, recent efforts with cabozantinib, CLDN6 inhibition and the role of maintenance chemotherapy with or without tyrosine kinase inhibition (TKIs) in patients after HDCT.