Testicular germ cell tumors (TGCTs) are a model for curable cancer because of exquisite chemosensitivity and incorporation of multimodal therapy. Nevertheless, our ability to predict metastases in early-stage disease and responders to chemotherapy in advanced disease is limited. Treatment options for cisplatin-resistant disease are sparse. A further understanding of TGCT biology may allow for more precise patient counseling and identify novel therapies in patients with cisplatin-resistant disease.
Adult TGCTs are characterized by frequent chromosomal anomalies and low rates of somatic mutations. Large-scale integrated molecular analysis of early-stage TGCT patients is actively underway. In addition to ubiquitous gain of isochromosome 12p, current molecular studies have confirmed mutations of previously described genes (i.e., KIT and KRAS) and described novel mutations. Analysis of cisplatin-resistant cases has identified high rates of alterations within the TP53-MDM2 axis and a high proportion of patients with potentially actionable targets, including TP53-MDM2, PI3 kinase, and MAPK signaling pathway alterations. The role of epigenetics in TGCT development and prognosis is also being further characterized.
Further molecular characterization of TGCT may allow for avoidance of unnecessary treatment in patients with early-stage disease and also provide new treatment options in patients with cisplatin-resistant disease.
Current opinion in urology. 2016 Aug 31 [Epub ahead of print]
Solomon L Woldu, James F Amatruda, Aditya Bagrodia
University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.