Drug combinations of camptothecin derivatives promote the antitumor properties

Abstract

Camptothecin (CPT) derivatives are widely used as small molecule chemotherapeutic agents and have demonstrated efficacy in the treatment of diverse solid tumors. A variety of derivatives have been developed to resolve the drawbacks of poor water solubility, high toxicity and rapid hydrolysis in vivo. However, the obstacles, such as acquired resistance and toxicity, still exist. The utilization of rational drug combinations has the potential to enhance the efficacy and mitigate the toxicity of CPT derivatives. This paper provides an overview of CPT derivatives in combination with other drugs, with a particular focus on cell cycle inhibitors, DNA synthesis inhibitors, anti-metastatic drugs and immunotherapy agents. Concurrently, the mechanisms of antitumor activity of combinations of different classes of drugs and CPT derivatives are elucidated. While the various combination strategies have yielded more favorable therapeutic outcomes, the efficacy and toxicity of the drug combinations are influenced by the inherent properties of the drugs involved. Moreover, a summary of the drug conjugates of CPT derivatives was provided, accompanied by an analysis of the structural activity relationship (SAR). This paves the way for the subsequent developments in drug combinations and delivery modes.