BRCA1 Gene as a Potential Marker for Lung Cancer Therapy

DNA double-strand breaks (DSBs), caused by various endogenous and exogenous factors, pose a significant threat to genomic stability. Several conserved repair pathways address DSBs, with homologous recombination (HR) being the only mechanism capable of accurately restoring the original DNA sequence. The BRCA1 gene plays a critical role in HR and is involved in maintaining genomic stability, cell cycle regulation, transcription, and tumor angiogenesis. Germline mutations in BRCA1 are strongly associated with increased risks of breast, ovarian, and other cancers. Dysfunction of BRCA1 leads to homologous recombination deficiency (HRD), forcing cells to rely on error-prone repair pathways, which promotes genomic instability and tumorigenesis. Besides hereditary mutations, HRD can also arise in sporadic cancers through epigenetic mechanisms such as promoter hypermethylation and reduced BRCA1 expression. Although BRCA1 deficiency is uncommon in lung cancer, BRCA1 status is considered a potential biomarker for sensitivity to platinum-based chemotherapy and other cytotoxic agents used in lung cancer treatment. However, the impact of BRCA1 on treatment response and prognosis in lung cancer remains controversial and not fully understood. This review summarizes current evidence on the role of BRCA1 in modulating chemotherapy response and disease outcomes in lung cancer patients, highlighting its potential as a biomarker for personalized therapy selection. Thus, in this context, the key unresolved issues critical for the development of personalized treatment strategies for lung cancer associated with BRCA1 alterations include the identification of molecular biomarkers most reliably associated with tumor sensitivity to chemotherapy. In addition, the development of methods for identifying patients with homologous recombination deficiency specifically in lung tumors appears to be of considerable importance, as does a better understanding of how the biological and therapeutic implications of BRCA1-related parameters in lung cancer differ from those observed in other tumor types. Addressing these challenges could substantially improve the efficacy of chemotherapy and patient outcomes, while also expanding the opportunities for a personalized approach to treatment selection in patients with lung cancer.