2. Academic Validation
  3. Functional characterization of CFI-400945, a Polo-like kinase 4 inhibitor, as a potential anticancer agent

Functional characterization of CFI-400945, a Polo-like kinase 4 inhibitor, as a potential anticancer agent

  • Cancer Cell. 2014 Aug 11;26(2):163-76. doi: 10.1016/j.ccr.2014.05.006.
Jacqueline M Mason 1,  Dan Chi-Chia Lin 1,  Xin Wei 1,  Yi Che 1,  Yi Yao 1,  Reza Kiarash 1,  David W Cescon 2,  Graham C Fletcher 1,  Donald E Awrey 1,  Mark R Bray 1,  Guohua Pan 1,  Tak W Mak 3
Affiliations

Affiliations

  • 1 The Campbell Family Institute for Breast Cancer Research, 101 College Street, Toronto, ON M5G 1L7, Canada.
  • 2 The Campbell Family Institute for Breast Cancer Research, 620 University Avenue, Toronto, ON M5G 2M9, Canada.
  • 3 The Campbell Family Institute for Breast Cancer Research, 620 University Avenue, Toronto, ON M5G 2M9, Canada. Electronic address: tmak@uhnres.utoronto.ca.
PMID: 25043604 DOI: 10.1016/j.ccr.2014.05.006
Abstract

PLK4 was identified as a promising therapeutic target through a systematic approach that combined RNAi screening with gene expression analysis in human breast cancers and cell lines. A drug discovery program culminated in CFI-400945, a potent and selective PLK4 Inhibitor. Cancer cells treated with CFI-400945 exhibit effects consistent with PLK4 kinase inhibition, including dysregulated centriole duplication, mitotic defects, and cell death. Oral administration of CFI-400945 to mice bearing human Cancer xenografts results in the significant inhibition of tumor growth at doses that are well tolerated. Increased antitumor activity in vivo was observed in PTEN-deficient compared to PTEN wild-type Cancer xenografts. Our findings provide a rationale for the clinical evaluation of CFI-400945 in patients with solid tumors, in particular those deficient in PTEN.

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