BRCA1-MTOR CROSSTALK IN BREAST CANCER

Abstract

Breast cancer arises from the interplay of genomic stability pathways and metabolic signaling networks. The tumor suppressor BRCA1, which plays a critical role in regulating DNA damage repair, and the mechanistic target of rapamycin (mTOR), which regulates cell growth and metabolism, have generally been studied However, growing evidence suggests a functional cross-talk between BRCA1 and mTOR signaling in breast cancer. BRCA1 deficiency not only impairs homologous recombination-based DNA repair but also stimulates mTOR signaling by suppressing the PI3K/AKT pathway, resulting in increased anabolic Conversely, mTOR signaling can regulate BRCA1 function by post-translationally modifying it and through stress responses, indicating a bidirectional regulation This review summarizes the current understanding of mechanistic insights of the BRCA1-mTOR signaling interface focusing on key regulatory nodes, feedback loops and context-dependent interactions. We also discuss the therapeutic potential of blocking this crosstalk, including PARP inhibitor and mTOR inhibitor combinations. Knowing this integrated signaling network may lead to new mechanism-based treatments in breast cancer.