Mitotic checkpoint defects in human cancers and their implications to chemotherapy (original) (raw)

IMR Press / FBL / Volume 13 / Issue 6 / DOI: 10.2741/2827

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article

Mitotic checkpoint defects in human cancers and their implications to chemotherapy

Affiliation

1 Department of Anatomy, Faculty of Medicine, The University of Hong Kong, Hong Kong

2 Department of Biochemistry, Faculty of Medicine, The University of Hong Kong, Hong Kong

*Author to whom correspondence should be addressed.

Published: 1 January 2008

Abstract

The mitotic checkpoint, also known as spindle assembly checkpoint, is to ensure accurate chromosome segregation by inducing mitotic arrest when errors occur in the spindle structure or in the alignment of the chromosomes on the spindle. Loss of mitotic checkpoint control is a common event in human cancer cells, which is thought to be responsible for chromosome instability frequently observed in cancer cells. Several reports have shown that cells with a defective mitotic checkpoint are more resistant to several types of anticancer drugs from microtubule disruptors to DNA damaging agents. In addition, inactivation of key mitotic checkpoint proteins such as BUB (budding uninhibited by benzimidazole) and MAD (mitotic arrest deficient) is influential in drug resistance in mitotic checkpoint defective cancer cells. The mitotic checkpoint has also been linked to DNA damage response and a defective mitotic checkpoint confers cancer cells resistance to certain DNA damaging anticancer drugs. This review presents recent evidence on mitotic checkpoint defects in human cancers and their association with resistance to anticancer drugs. In addition, the clinical importance and potential therapeutic implications of targeting the mitotic checkpoint to reverse drug resistance in cancer cells are also discussed.

Front. Biosci. (Landmark Ed) Print ISSN 2768-6701 Electronic ISSN 2768-6698

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