Polo-like kinase 1 inhibitors and their potential role in anticancer therapy, with a focus on NSCLC.

Abstract

Cytotoxic platinum-doublet chemotherapy that includes antimitotic agents is a current standard of care in advanced non-small cell lung cancer (NSCLC). Microtubule-targeting antimitotics, taxanes, and Vinca alkaloids are effective anticancer therapeutics that affect both dividing and nondividing cells. A new generation of antimitotic agents that target regulatory proteins-mitotic kinases and kinesins-has the potential to overcome the limitations related to the role of tubulin in nondividing cells that are associated with traditional antimitotics. This review concentrates on Polo-like kinase 1, a key regulator of mitosis, outlines a rationale for its development as an anticancer target, and discusses data from preclinical and clinical studies of Plk1 inhibitors with a particular focus on NSCLC.