A Possible Target in Triple-Negative Breast Cancer

Studies have shown that a fraction of triple-negative breast cancers (TNBCs) have activating mutations in PIK3CA or AKT1 and decreased expression in PTEN, which can lead to activation of the AKT pathway. To date, clinical trials with PIK3CA inhibitors in breast cancer have shown only modest activity. However, the oral ATP-competitive small-molecule AKT inhibitor ipatasertib has shown activity across a broad range of malignancies in preclinical models. Moreover, synergy has been demonstrated by combining ipatasertib with paclitaxel in preclinical models, and a phase I trial of ipatasertib demonstrated an acceptable safety profile and evidence of antitumor activity in previously treated patients with a variety of malignancies (Clin Cancer Res…