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Review

Role of Nucleotide Excision Repair in Cisplatin Resistance

1
Comprehensive Cancer Center, Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USA
2
Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM 87131, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(23), 9248; https://doi.org/10.3390/ijms21239248
Received: 31 October 2020 / Revised: 27 November 2020 / Accepted: 30 November 2020 / Published: 4 December 2020
Cisplatin is a chemotherapeutic drug used for the treatment of a number of cancers. The efficacy of cisplatin relies on its binding to DNA and the induction of cytotoxic DNA damage to kill cancer cells. Cisplatin-based therapy is best known for curing testicular cancer; however, treatment of other solid tumors with cisplatin has not been as successful. Pre-clinical and clinical studies have revealed nucleotide excision repair (NER) as a major resistance mechanism against cisplatin in tumor cells. NER is a versatile DNA repair system targeting a wide range of helix-distorting DNA damage. The NER pathway consists of multiple steps, including damage recognition, pre-incision complex assembly, dual incision, and repair synthesis. NER proteins can recognize cisplatin-induced DNA damage and remove the damage from the genome, thereby neutralizing the cytotoxicity of cisplatin and causing drug resistance. Here, we review the molecular mechanism by which NER repairs cisplatin damage, focusing on the recent development of genome-wide cisplatin damage mapping methods. We also discuss how the expression and somatic mutations of key NER genes affect the response of cancer cells to cisplatin. Finally, small molecules targeting NER factors provide important tools to manipulate NER capacity in cancer cells. The status of research on these inhibitors and their implications in cancer treatment will be discussed. View Full-Text
Keywords: DNA damage; chemotherapy; XPA; ERCC1-XPF; CSB DNA damage; chemotherapy; XPA; ERCC1-XPF; CSB
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MDPI and ACS Style

Duan, M.; Ulibarri, J.; Liu, K.J.; Mao, P. Role of Nucleotide Excision Repair in Cisplatin Resistance. Int. J. Mol. Sci. 2020, 21, 9248. https://doi.org/10.3390/ijms21239248

AMA Style

Duan M, Ulibarri J, Liu KJ, Mao P. Role of Nucleotide Excision Repair in Cisplatin Resistance. International Journal of Molecular Sciences. 2020; 21(23):9248. https://doi.org/10.3390/ijms21239248

Chicago/Turabian Style

Duan, Mingrui; Ulibarri, Jenna; Liu, Ke J.; Mao, Peng. 2020. "Role of Nucleotide Excision Repair in Cisplatin Resistance" Int. J. Mol. Sci. 21, no. 23: 9248. https://doi.org/10.3390/ijms21239248

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