DNA damage repair (DDR) pathways are essential to ensure the accurate transmission of genetic material. However, different endogenous and exogenous factors challenge genomic integrity. Mechanisms involved in the alterations of DDR pathways mainly include genetic inactivation and epigenetic mechanisms. The development and progression of
carcinomas are closely associated with DDR pathway aberrations, including the epigenetic silencing of gene O6-alkylguanine-DNA
methyltransferase (MGMT); deficiencies of mismatch repair (MMR) genes, including
MutL homolog 1 (MLH1),
MutS protein homologue (MSH)-2 (MSH2), MSH6, and PMS1 homolog 2; the mismatch repair system component (PMS2); and mutations of homologous recombination repair (HRR) genes, such as the
breast cancer susceptibility gene 1/2 (BRCA1/2). Understanding the underlying mechanisms and the correlations between alterations to DDR pathways and
cancer could improve the efficacy of antitumor
therapies. Emerging evidence suggests that survival is higher in patients with DDR-deficient
tumors than in those with DDR-proficient
tumors. Thus, DDR alterations play a predictive and prognostic role in anticancer
therapies. Theoretical studies on the co-administration of DDR inhibitors and other anticancer
therapies, including
chemotherapy,
radiotherapy,
immunotherapy, endocrine
therapy, and epigenetic drugs, hold promise for
cancer treatments. In this review, we focus on the basic mechanisms, characteristics, current applications, and combination strategies of DDR pathways in the anticancer field.