Molecular bases of platinum-resistance in testicular cancer

• Published in: Archivos españoles de urología Vol. 66; no. 5; pp. 524 - 535
• Main Authors: Germà-Lluch, Josep Ramon, Piulats, Josep Maria
• Format: Journal Article
• Language: Spanish
• Published: Spain 01-06-2013
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Cisplatin - pharmacology; Cisplatin - therapeutic use; DNA, Neoplasm - drug effects; Drug Resistance, Neoplasm - genetics; Humans; Male; Molecular Biology; Platinum - therapeutic use; Teratoma - drug therapy; Teratoma - genetics; Testicular Neoplasms - drug therapy; Testicular Neoplasms - genetics
• ISSN: 1576-8260

Cisplatin has been the cornerstone of germ cell testicular tumors therapy since its introduction more tan 30 years ago, and a basic part of the schemes given to multiple ovarian, lung, head and neck, and bladder tumors among others. Some tumors present primary resistance to this drug, others will develop it despite good initial response. In the case of testicular germ cell tumors most of them are very sensitive to this drug but up to 20% of patients with metastatic disease will present resistance, most of them secondary after a very good initial response. Cisplatin acts by binding to DNA to activate genetic damage recognition mechanisms and apoptosis through the mitochondrial pathway. Resistance mechanisms to cisplatin have been classified in those that happen (1) before its binding to DNA and (2) once it binds to DNA. Most advances in their discovery have used other neoplasias as models, mainly ovarian and lung tumors. In this review we will describe the biological mechanisms behind resistance to cisplatin from the global perspective but trying to focus in testicular germ cell tumors.