Platinum compounds 30 years after the introduction of cisplatin: Implications for the treatment of ovarian cancer

Cisplatin and carboplatin have dominated the drug therapy of ovarian cancer and other gynecologic malignancies during the past three decades. This review, based on a recent international conference on metal coordination compounds, highlights advances in our understanding of their mechanisms of action and resistance. Two emerging areas are of special importance: 1) the role of transporters and exporters (first identified in the regulation of copper) in imparting the special selectivity of platinum drugs (also including oxaliplatin) for specific tumors; and 2) the relevance of inactivated DNA repair pathways, and in particular those related to BRCA genes in determining sensitivity of tumors to platinum drugs. The status of DNA repair pathways may become relevant to response to platinums and to the treatment of ovarian cancer in general: repair inhibitors are under testing alone or in combination with cytotoxic drugs for cancer.