PI3K-AKT-mTOR Pathway Cooperates with the DNA Damage Repair Pathway: Carcinogenesis in Triple-Negative Breast Cancers and Beyond

Understanding of the biology of tumor cells of breast cancers like most of other solid tumors has undergone an evolutionary change at the molecular level with the advent of exome sequencing or whole genome sequencing technology. In today’s “clinic to laboratory and back” culture of medical practice, the genomics alteration-driven (biomarker) approach to cancer treatment has not only provided a better justification for the treatment of breast cancers but also added an invaluable tool for the diagnosis of “cancer evolution” and its therapeutic management. Recognizing the fact that the PI3K-mTOR pathway is a master regulator of tumor cell survival, proliferation, nutrient sensor, protein translation, metabolism, metastasis-associated phenotypes and angiogenesis, the PI3K pathway has been explored as one of the most studied targets in cancers. We here evaluated merits of the combination of DNA damage repair pathway inhibitor(s) with inhibitor(s) of the PI3K-mTOR pathway in targeting basal-like and triple-negative breast cancers. Sensitizing triple-negative breast cancer cells to inhibitors of DNA damage repair pathway by inhibitors of PI3K-mTOR pathway has been comprehensively discussed in the light of recent studies demonstrating that PI3K-AKT-mTOR pathway closely cooperates with the DNA damage repair pathway.