PI3K/AKT/mTOR signaling pathway: an important driver and therapeutic target in triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) is a highly heterogeneous tumor lacking estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. It has higher aggressiveness and metastasis than other subtypes, with limited effective therapeutic strategies, leading to a poor prognosis. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway is prevalently over-activated in human cancers and contributes to breast cancer (BC) growth, survival, proliferation, and angiogenesis, which could be an interesting therapeutic target. This review summarizes the PI3K/AKT/mTOR signaling pathway activation mechanism in TNBC and discusses the relationship between its activation and various TNBC subtypes. We also report the latest clinical studies on kinase inhibitors related to this pathway for treating TNBC. Our review discusses the issues that need to be addressed in the clinical application of these inhibitors.

mTOR: Its Critical Role in Metabolic Diseases, Cancer, and the Aging Process

“…mTOR has been reported to be dysregulated in approximately 70% of breast cancers [ 49 ]. Triple-negative breast cancer (TNBC), a form of breast cancer that is more aggressive and has a higher susceptibility for metastases, has been reported to have mutations in the PI3K/Akt/mTOR pathway in 25% of cases [ 50 , 51 ]. Such disruption serves as a key TNBC survival and resistance-coping mechanism, making it a promising target for the treatment of TNBC.…”