Expert consensus on the clinical application of PI3K/AKT/mTOR inhibitors in the treatment of advanced breast cancer

Abstract

Phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB or AKT)/ mammalian target of rapamycin (mTOR) signaling pathway (PAM pathway) plays an important role in the development of breast cancer and are closely associated with the resistance to endocrine therapy in advanced breast cancer. Therefore, anticancer treatment targeting key molecules in this signaling pathway has become a research hotspot in recent years.Randomized clinical trials have demonstrated that PI3K/AKT/mTOR inhibitors bring significant clinical benefit to patients with advanced breast cancer, especially to those with hormone receptor (HR)-positive, human epidermal growth factor receptor (HER) 2-negative advanced breast cancer. Alpelisib, a PI3K inhibitor, and everolimus, an mTOR inhibitor, have been approved by FDA. Based on their high efficacy and relatively good safety profile, an expanded indication of everolimus in breast cancer has been approved by National Medical Products Administration (NMPA). Alpelisib is expected to be approved in China in the near future. The members of the consensus expert panel reached this consensus to comprehensively define the role of PI3K/AKT/mTOR signaling pathway in breast cancer, efficacy

New Emerging Targets in Cancer Immunotherapy: The Role of B7-H3

“…Importantly, constitutive activation of the mTOR pathway is also pertinent to BC progression, as its activation promotes anabolism [ 139 ] and confers enhanced proliferation and metastatic potential [ 140 ]. PI3K/Akt/mTOR inhibitors comprise a validated treatment modality, especially for hormone receptor positive/HER2 negative disease [ 141 ]. B7-H3 overexpressing BC cells were found to be less susceptible to the effects of the PI3K/Akt/mTOR pathway inhibitors, triciribidine and everolimus, compared to B7-H3 knock-out counterparts [ 142 ].…”