Strategic Combinations of Aurora Kinase an Inhibiton with Targeted Drugs for Synergistic Anti-Tumor Effect

Abstract

Inhibition of mitosis is an established therapeutic approach in the treatment of cancer. However, existing drugs that use this mechanism including taxanes cause off-target effects leading to dose-limiting toxicity such as sensory neuropathy. Development of inhibitors of mitosis-specific targets has created the next generation of mitosis inhibitors with the goal of achieving similar anti-tumor efficacy but with less toxicity. Aurora Kinase A is one example of a mitosis-specific target for which multiple drugs have been developed as anti-cancer therapy. Although early preclinical studies have showed on-target effects, clinical development has been slowed by minimal efficacy as monotherapy. However, strategic combinations of Aurora Kinase A inhibition with various targeted drugs has shown promise and led to renewed interest in the potential of inhibiting this mitosis-specific target.