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Erschienen in: Journal of Cancer Research and Clinical Oncology 10/2019

06.09.2019 | Review – Cancer Research

PLK4: a promising target for cancer therapy

verfasst von: Yi Zhao, Xin Wang

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 10/2019

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Abstract

Purpose

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.

Methods

The relevant literature from PubMed is reviewed in this article. The ClinicalTrials.gov database was searched for clinical trials related to the specific topic.

Results

PLK4 is aberrantly expressed in multiple cancers and has prognostic value. Targeting PLK4 with inhibitors suppresses tumor growth in vitro and in vivo.

Conclusions

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.
Literatur
Zurück zum Zitat Chan JY (2011) A clinical overview of centrosome amplification in human cancers. Intern J Biol Sci 7:1122–1144CrossRef Chan JY (2011) A clinical overview of centrosome amplification in human cancers. Intern J Biol Sci 7:1122–1144CrossRef
Zurück zum Zitat Li J, Tan M, Li L, Pamarthy D, Lawrence TS, Sun Y (2005) SAK, a new polo-like kinase, is transcriptionally repressed by p53 and induces apoptosis upon RNAi silencing. Neoplasia 7:312–323CrossRefPubMedPubMedCentral Li J, Tan M, Li L, Pamarthy D, Lawrence TS, Sun Y (2005) SAK, a new polo-like kinase, is transcriptionally repressed by p53 and induces apoptosis upon RNAi silencing. Neoplasia 7:312–323CrossRefPubMedPubMedCentral
Zurück zum Zitat Marina M, Saavedra HI (2014) Nek2 and Plk4: prognostic markers, drivers of breast tumorigenesis and drug resistance. Front Biosci (Landmark Ed) 19:352–365CrossRef Marina M, Saavedra HI (2014) Nek2 and Plk4: prognostic markers, drivers of breast tumorigenesis and drug resistance. Front Biosci (Landmark Ed) 19:352–365CrossRef
Zurück zum Zitat Pihan GA, Wallace J, Zhou Y, Doxsey SJ (2003) Centrosome abnormalities and chromosome instability occur together in pre-invasive carcinomas. Cancer Res 63:1398–1404PubMed Pihan GA, Wallace J, Zhou Y, Doxsey SJ (2003) Centrosome abnormalities and chromosome instability occur together in pre-invasive carcinomas. Cancer Res 63:1398–1404PubMed
Metadaten
Titel
PLK4: a promising target for cancer therapy
verfasst von
Yi Zhao
Xin Wang
Publikationsdatum
06.09.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 10/2019
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-019-02994-0

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