Chapters authored
Translational Challenges and Therapeutic Opportunities in BRCA1-Related Breast Cancer
Although significant progress has been made in the management of the hereditary cancer syndrome related to mutations of BRCA1, two fundamental and clinically relevant questions regarding BRCA1-related cancer syndrome remain unresolved: (1) What factors account for the tissue specificity of the BRCA1-related cancer risk? (2) How does a mutation or loss of BRCA1 lead to the basal-like phenotype of breast cancer? This review focuses on recent studies in BRCA1-related pathways that lead to specific characteristics of the hereditary cancer syndrome and discusses the current translational evidence for exploiting these pathways in new therapeutic strategies. Mounting evidence suggests that estrogen signaling and metabolism, oxidative stress, specific secondary mutations, and regulation of specific progenitor cells and transcriptional programs are critical in BRCA1-associated breast cancer. Strategies geared toward estrogen reduction may play a role in treatment and prevention. Therapies aimed at mitigating oxidative stress may be a strategy for risk reduction, while cancer-cell-specific sensitivity to oxidative stress may also be an opportunity for specific targeting. BRCA1-related transcriptional regulation and signaling provide a number of therapeutic targets, including the PI3-AKT and Notch pathways. Thus, significant opportunities exist in translational and clinical research for developing the treatment strategies for the management of BRCA1-related breast cancer.
Part of the book: Breast Cancer