New Molecular Mechanisms of Action of Camptothecin-type Drugs

Abstract

Camptothecin (CPT) derivatives have emerged as a promising group of chemotherapeutic agents. The FDA has approved the CPT derivatives topotecan and irinotecan for second line treatment of ovarian cancer and metastatic colorectal cancer, respectively. These and other CPT derivatives have become part of the multi-million dollar industry that is dedicated to finding better chemotherapeutic agents with excellent tumor kill and less normal tissue toxicity. In order to reach this goal it is imperative to understand the details of the mechanisms of action and the targets of these drugs, as well as the cellular response to the drugs. Although investigations of CPT date back to the 1960's, most of the studies that have been added to our present knowledge were done in the last 10 years. The purpose of this paper is to review the latest insights into the CPT binding site, CPT-induced gene expression and CPT-induced pathways to apoptosis.