PLK4: a promising target for cancer therapy
Polo-like kinase 4 (PLK4) is a serine/threonine protein kinase that regulates centriole duplication. PLK4 deregulation causes centrosome number abnormalities, mitotic defects, chromosomal instability and, consequently, tumorigenesis. Therefore, PLK4 has emerged as a therapeutic target for the treatment of multiple cancers. In this review, we summarize the critical role of centrosome amplification and PLK4 in cancer. We also highlight recent advances in the development of PLK4 inhibitors and discuss potential combination therapies for cancer.
The relevant literature from PubMed is reviewed in this article. The ClinicalTrials.gov database was searched for clinical trials related to the specific topic.
PLK4 is aberrantly expressed in multiple cancers and has prognostic value. Targeting PLK4 with inhibitors suppresses tumor growth in vitro and in vivo.
PLK4 plays an important role in centrosome amplification and tumor progression. PLK4 inhibitors used alone or in combination with other drugs have shown significant anticancer efficacy, suggesting a potential therapeutic strategy for cancer. The results of relevant clinical trials await evaluation.
KeywordsPLK4 Centrosomes PLK4 inhibitor CFI-400945 Cancer
This study was funded by National Natural Science Foundation (No. 81270598, No. 81473486, and No. 81770210); Key Research and Development Program of Shandong Province (No. 2018CXGC1213); Technology Development Projects of Shandong Province (No. 2017GSF18189); Taishan Scholar Foundation of Shandong Province; Shandong Provincial Engineering Research Center of Lymphoma; Key Laboratory for Kidney Regeneration of Shandong Province.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
Statement of human and animal rights
This article does not contain any studies with human participants or animals performed by any of the authors.
Human participants were not involved in the study.
- Pihan GA, Wallace J, Zhou Y, Doxsey SJ (2003) Centrosome abnormalities and chromosome instability occur together in pre-invasive carcinomas. Cancer Res 63:1398–1404Google Scholar
- Wu J, Akhmanova A (2017) Microtubule-Organizing Centers. Annu Rev Cell Dev Biol 33:51–75. https://doi.org/10.1146/annurev-cellbio-100616-060615 CrossRefGoogle Scholar