Development of new cancer therapeutic agents targeting mitosis

Abstract

Targeting cellular proliferation persists as a mainstay of cancer therapeutic strategy. Although microtubule-targeting drugs (such as taxanes and vinca alkaloids) have been used successfully in the clinic to treat a variety of cancers, they carry substantial liabilities that have spurred drug companies to aggressively pursue new tubulin-targeting drug candidates with improved efficacy and toxicity profiles. The recent discoveries of new mitotic targets for cancer therapy (such as kinesin spindle protein, Aurora kinases and Polo-like kinase-1) have also stimulated intense work focused on identifying novel antimitotic drugs directed at these new targets. A number of novel antimitotic drugs have demonstrated encouraging activity in preclinical models and have progressed into clinical development. This review focuses on selected new antimitotic drugs under evaluation in clinical trials.

Keywords::

• antimitotic agent
• Aurora kinase
• blood–brain barrier
• cancer chemotherapy
• epothilone
• kinesin
• microtubule
• mitosis
• mitotic spindle
• multi-drug resistance
• P-glycoprotein
• Polo-like kinase
• taxane
• tubulin
• vinca alkaloid

Notes