Genetic Variants in DNA Repair Pathways: Implications for Platinum-Based Chemotherapy in Breast Cancer

Breast cancer poses a significant global health challenge, with platinum-based chemotherapy playing a crucial role in treatment protocols. Agents like cisplatin and carboplatin exert their therapeutic effects by inducing DNA damage through intra- and inter-strand crosslinks, triggering apoptosis in cancer cells. However, the efficacy of platinum chemotherapy varies widely due to genetic variations in DNA repair pathways. This review explores the impact of genetic variants in DNA repair genes on the response to platinum-based chemotherapy in breast cancer. Key pathways such as Base Excision Repair (BER), Nucleotide Excision Repair (NER), and Homologous Recombination (HR) are essential for repairing platinum-induced DNA damage. Specific genetic polymorphisms, including XRCC۱ codon ۳۹۹, ERCC۲ Lys۷۵۱Gln, and ERCC۱ variants, have been associated with altered repair capacities and clinical outcomes in response to platinum agents. Studies have highlighted that breast cancer patients with BRCA۱ or BRCA۲ mutations exhibit increased sensitivity to platinum salts, suggesting potential for targeted therapy in this subgroup. Additionally, polymorphisms in XPD (ERCC۲) and XRCC۳ have shown associations with survival outcomes in response to platinum-based treatments. Pharmacogenetic analyses are crucial for identifying patients likely to benefit from platinum chemotherapy based on their genetic profiles. Understanding these genetic variants not only aids in predicting treatment responses but also guides personalized treatment strategies to enhance efficacy and minimize toxicity. Breast cancer remains a formidable challenge worldwide, demanding continued advancements in treatment strategies to improve patient outcomes. Platinum-based chemotherapy, comprising agents like cisplatin and carboplatin, stands as a cornerstone in the therapeutic arsenal against breast cancer by inducing DNA damage through intricate mechanisms of intra- and inter-strand crosslink formation. This approach disrupts cancer cell replication and triggers programmed cell death, contributing significantly to treatment efficacy. The variability in treatment response observed among breast cancer patients undergoing platinum chemotherapy underscores the pivotal role of genetic variations in DNA repair pathways. Insights into Base Excision Repair (BER), Nucleotide Excision Repair (NER), and Homologous Recombination (HR) pathways reveal how specific genetic polymorphisms can influence repair capabilities and, consequently, clinical outcomes. Notably, variants such as XRCC۱ codon ۳۹۹, ERCC۲ Lys۷۵۱Gln, and ERCC۱ mutations have been implicated in altering response profiles to platinum agents, thereby affecting treatment efficacy and patient survival. Moreover, the identification of BRCA۱ and BRCA۲ mutations as predictors of enhanced sensitivity to platinum salts underscores the potential for targeted therapeutic interventions in this genetically defined subgroup of breast cancer patients. Pharmacogenetic profiling emerges as a critical tool in tailoring treatment strategies, enabling clinicians to optimize therapeutic regimens based on individual genetic profiles and thereby enhance treatment outcomes while minimizing adverse effects. In conclusion, genetic variants in DNA repair pathways serve as promising indicators of treatment response and outcomes in breast cancer patients treated with platinum-based chemotherapy. Embracing these insights promises to usher in a new era of personalized medicine, where tailored therapies based on genetic profiles pave the way for improved patient outcomes and enhanced quality of life.

کلیدواژه ها:

Breast cancer ، Platinum-based chemotherapy ، DNA repair pathways ، Genetic variants ، Pharmacogenetics