Mechanisms of cisplatin resistance: DNA repair and cellular implications

Adams, Mark N., Ashton, Nicholas W., Paquet, Nicolas, O'Byrne, Kenneth J., & Richard, Derek J. (2014) Mechanisms of cisplatin resistance: DNA repair and cellular implications. In Morais, Christudas (Ed.) Advances in Drug Resistance Research. Nova Science Publishers, New York, pp. 1-37.

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Abstract

Cisplatin (cis-diamminedichloroplatinum (II)), is a platinum based chemotherapeutic employed in the clinic to treat patients with lung, ovarian, colorectal or head and neck cancers. Cisplatin acts to induce tumor cell death via multiple mechanisms. The best characterized mode of action is through irreversible DNA cross-links which activate DNA damage signals leading to cell death via the intrinsic mitochondrial apoptosis pathway. However, the primary issue with cisplatin is that while patients initially respond favorably, sustained cisplatin therapy often yields chemoresistance resulting in therapeutic failure. In this chapter, we review the DNA damage and repair pathways that contribute to cisplatin resistance. We also examine the cellular implications of cisplatin resistance that may lead to selection of subpopulations of cells within a tumor. In better understanding the mechanisms conferring cisplatin resistance, novel targets may be identified to restore drug sensitivity.

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ID Code: 84730
Item Type: Book Chapter
Keywords: Cisplatin Resistance, Interstrand cross-links, DNA repair, tumor-initiating cell
ISBN: 9781631171314
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2014 Nova Science Publishers Inc.
Deposited On: 11 Jun 2015 22:57
Last Modified: 18 Apr 2017 04:05

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