Overcome cancer drug resistance by targeting epigenetic modifications of centrosome.

Zan-Hui Jia,Hong Zhang,Xing-Gang Wang

doi:10.20517/cdr.2018.010

Zan-Hui Jia, Hong Zhang + Show 1 more

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https://doi.org/10.20517/cdr.2018.010

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Journal: Cancer drug resistance	Publication Date: Jan 1, 2019
Citations: 6	License type: cc-by

Affiliation: Jilin University, University of Basel

Abstract

The centrosome is an organelle that serves as the microtubule- and actin-organizing center of human cells. Although the centrosome is small of size, it is great important on cellular function that regulates cytoskeletal organization and governs precise spindle orientation/positioning ensuring equal distribution of cellular components in cell division. Epigenetic modifications to centrosome proteins can lead to centrosome aberrations, such as disorganized spindles and centrosome amplification causing aneuploidy and genomic instability. Epigenetic disturbances are associated not only with carcinogenesis and cancer progression, but also with drug resistance to chemotherapy. In this review, we discuss mechanisms of epigenetic alteration during the centrosome biogenesis in cancer. We provide an update on the current status of clinical trials that aim to target epigenetic modifications in centrosome aberrations and to thwart drug resistance.

Highlights

It has long been considered that the accumulation of genetic mutations in tumor suppressors and/or oncogenes causes cancer[1]
We discuss in detail on centrosome structure, aberrations of centrosome in cancer, the relationship of cancer drug resistance to centrosome amplification and new drug development
Ref. [34] [32] [33] [35] [36,37] [38,39,40] [41,42,43] [44,45] [46] [47]. These studies indicate that centrosome aberrations produce aneuploidy, chromosome instability leading to tumorigenesis and promote cancer drug resistance

Summary

Introduction

It has long been considered that the accumulation of genetic mutations in tumor suppressors and/or oncogenes causes cancer[1]. These studies indicate that centrosome aberrations produce aneuploidy, chromosome instability leading to tumorigenesis and promote cancer drug resistance. Overexpression of Aurora-A kinase induces centrosome amplification and chromosomal instability that create tumor cell heterogeneity, is associated with acquired drug resistance[56].

Results

Conclusion