Therapeutic Potential of Phenols as PI3K-AKT and mTOR Inhibitors in Breast Cancer and its Molecular Pathogenesis

Introduction: Breast cancer is the second leading cause of cancer-related death, affecting 2.3 million people every year with high recurrence and metastasis. From Halsted’s mastectomy to modern chemotherapeutic agents, various attempts have been made to combat breast cancer. Despite being effective, they are associated with chemoresistance and treatment-related adverse effects. This implicates a pressing need for novel chemotherapeutics that are costeffective with fewer side effects. Methods: Research articles were collected from the PubMed database. Articles were scanned by abstract and title for their relevance, and those deemed irrelevant were excluded. Only research articles focused on phenolic compounds to treat breast cancer in vitro and in vivo were included. Results: Naturally occurring phenolic compounds can inhibit tumor growth by acting on key signaling pathways. These compounds act as PI3K and AKT/PKB (Protein Kinase B) inhibitors. Discussion: PI3K (Phosphatidylinositol 3-kinase) mutations and overactivation of the PI3KAKT- mTOR (mammalian target of rapamycin) pathway are observed in breast cancer. Cancers with such PI3K mutations are more responsive to PI3K inhibitors. A PI3K inhibitor BYL719, in combination with fulvestrant, was recently approved by the FDA for use in estrogen receptor + and HER2- (Human epidermal growth factor receptor) breast cancer patients with PI3KCA mutations. Conclusion: This review explores phenolic compounds with the potential to target the PI3KAKT- mTOR pathway and discusses their mechanisms of action. Phenolic compounds like curcumin, quercetin, luteolin, apigenin, and resveratrol show effective antiproliferative and antimetastatic properties by acting on the PI3K pathway. Their therapeutic application in managing breast cancer is promising, with favourable and safe outcomes.