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

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Breast cancer remains a leading cause of cancer mortality in women, with significant heterogeneity.
• Acquired resistance to chemotherapy, such as doxorubicin (DOX), is a major clinical challenge.
• DNA damage repair (DDR) pathways play a critical role in the efficacy of chemotherapy and the development of drug resistance.

Purpose of the Study:

• To review the role of five major DNA repair pathways in doxorubicin (DOX) resistance in breast cancer.
• To provide a theoretical framework for understanding DDR mechanisms in DOX-resistant breast cancer.
• To guide future research and advance intervention strategies for resistant breast tumors.

Main Methods:

• Literature review focusing on the involvement of homologous recombination, nonhomologous end-joining, base excision repair, nucleotide excision repair, and mismatch repair.
• Analysis of the impact of these DDR pathways on doxorubicin (DOX) efficacy and resistance.
• Synthesis of current knowledge to establish a framework for future studies.

Main Results:

• Five major DNA repair pathways (homologous recombination, nonhomologous end-joining, base excision repair, nucleotide excision repair, and mismatch repair) are identified as key players in the development of DOX resistance.
• Understanding the specific roles of these pathways can elucidate mechanisms of resistance.
• Deficiencies in specific DDR pathways may present opportunities for targeted therapies.

Conclusions:

• DNA damage repair (DDR) pathways are pivotal in mediating breast cancer resistance to doxorubicin (DOX).
• Targeting specific DDR mechanisms in patients with defined repair deficiencies holds promise for personalized therapeutic approaches.
• This review provides a foundation for further research into DDR in DOX-resistant breast cancer, aiming to improve treatment outcomes.