DNA Damage Repair Pathways and Targeted Therapy for Doxorubicin-Resistant Breast Cancer.

Breast cancer, characterized by distinctive epidemiological patterns and substantial heterogeneity, continues to be among the leading causes of cancer-related mortality in women. As breast tumors progressively acquire resistance to doxorubicin (DOX), DNA damage repair (DDR) pathways are recognized as key determinants of both DOX efficacy and the onset of resistance. Targeting DDR mechanisms in breast cancer patients with specific repair deficiencies offers the potential for personalized therapeutic approaches. This review first discusses the pivotal roles of five major DNA repair pathways (homologous recombination, nonhomologous end-joining, base excision repair, nucleotide excision repair, and mismatch repair) in the development of DOX resistance. This review aims to establish a theoretical framework and reference for future studies on DDR mechanisms in DOX-resistant breast cancer to advance intervention strategies for resistant breast tumors and to promote further research in this area.