Nucleotide excision repair in tumor response to DNA-damaging anticancer therapies: a comprehensive review

Nucleotide excision repair (NER) is a critical DNA repair pathway responsible for removing bulky, helix-distorting DNA lesions, including ultraviolet radiation-induced photoproducts and platinum drug-DNA adducts. This review provides a comprehensive overview of current understanding of NER in cancer, with particular emphasis on its role in therapeutic response. We discuss the molecular mechanisms of DNA repair in cancer, the significance of NER in platinum-based therapies, results from in vitro studies across various cancer types, findings from patient-based studies, and outcomes from clinical trials. Special attention is given to ERCC1, ERCC2/XPD, XPA, and XPC molecules as potential biomarkers of treatment response and therapeutic targets, and incorporating the most recent discoveries regarding NER inhibitors, mutational signatures, and synthetic lethality-based approaches.