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Transl Oncol. 2015 Jun;8(3):185-95. doi: 10.1016/j.tranon.2015.03.010.

Targeting Polo-Like Kinases: A Promising Therapeutic Approach for Cancer Treatment.

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1
Purdue University, West Lafayette, IN, USA. Electronic address: liu8@purdue.edu.

Abstract

Polo-like kinases (Plks) are a family of serine-threonine kinases that regulate multiple intracellular processes including DNA replication, mitosis, and stress response. Plk1, the most well understood family member, regulates numerous stages of mitosis and is overexpressed in many cancers. Plk inhibitors are currently under clinical investigation, including phase III trials of volasertib, a Plk inhibitor, in acute myeloid leukemia and rigosertib, a dual inhibitor of Plk1/phosphoinositide 3-kinase signaling pathways, in myelodysplastic syndrome. Other Plk inhibitors, including the Plk1 inhibitors GSK461364A, TKM-080301, GW843682, purpurogallin, and poloxin and the Plk4 inhibitor CFI-400945 fumarate, are in earlier clinical development. This review discusses the biologic roles of Plks in cell cycle progression and cancer, and the mechanisms of action of Plk inhibitors currently in development as cancer therapies.

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