Mechanisms of resistance to platinum chemotherapeutic agents

Cis-platin and related compounds are some of the most powerful cytotoxic agents available for clinical use today. The effectiveness of such therapy is limited by the toxicity of the drugs, but more importantly by the existence of intrinsic or acquired resistance. As a result, the good responses seen when commencing platinum therapy are often short-lived. Relapse then occurs, as cell lines having intrinsic resistance or developing acquired resistance are selected out. These cells achieve resistance by three main mechanisms; prevention of drug accumulation, detoxification and DNA repair. The relative importance of each of these methods differs from cell line to cell line, and may even vary within a tumour, but in most cases it appears that the cell is dependent on a multifactorial mode of resistance. The understanding of these processes will hopefully allow the development of designer drugs which could overcome resistance, thereby improving success rates with platinum-based chemotherapy.