Discovery of Polo-like Kinase 4 Inhibitors for the Treatment of Cancer: A Mini Patent Review

Abstract: Polo-like kinase 4 (PLK4), a serine/threonine kinase, is a member of the PLK family. As a key regulator of the cell cycle, PLK4 controls centrosome duplication and mitosis. Abnormal PLK4’s function can induce centrosome amplification, leading to tumorigenesis, therefore, PLK4 has been regarded as a promising target for cancer therapy, and PLK4 inhibitors have potentials to treat multiple cancers and other PLK4-associated human disorders, such as myelodysplastic syndrome. In addition, PLK4 may function as a DNA-damage sensitizer, therefore improving the efficacy of chemotherapy. To date, some small-molecule inhibitors with different chemical scaffolds targeting PLK4 have been reported, among which, CFI-400945 has entered clinical trials for the treatment of various solid tumors, myeloid leukemia, and myelodysplastic syndrome. In this review, the structure and biological functions of PLK4 with other homologous PLKs are compared; the roles of PLK4 in different cancers are reviewed; and PLK4 inhibitors disclosed in patent or literature are summarized. Used alone or in combination with other anticancer drugs in preclinical and clinical studies, PLK4 inhibitors have shown significant efficacy in the treatment of different cancers, demonstrating that PLK4 could be a critical target for cancer diagnosis and therapy. However, our understanding of PLK4 is still limited, and novel mechanisms of PLK4 should be identified in future studies.