Chemosensitization to Platinum-Based Anticancer Drugs

Abstract

Cis-diamminedichloroplatinum (cisplatin or cis-DDP) is one of the most potent agents used in the chemotherapy of many cancers, including testes, ovary, head, neck, and lung. Cisplatin shows considerable efficacy in the treatment of testicular cancers with cure rates of greater than 90% (1). Despite its remarkable success in the treatment of cancer, its efficacy is limited by acquired or intrinsic resistance, and the mechanisms underlying chemoresistance are still under investigation. More importantly, novel strategies to reverse resistance and potentiate the antitumor action of cisplatin are actively being explored. Decreased cellular uptake and enhanced DNA repair activity are pointed to as the two major mechanisms of resistance to cisplatin (2–6). In this chapter, we will focus on DNA repair-mediated resistance to platinum-based drug and on current strategies to increase their potencies in refractory tumors. We will cover the newly explored crosstalk between DNA repair mechanisms and cell signaling as a target for tumor cell sensitization to platinated adducts.