Addressing the Mechanism of Action for the AKT Pathway in TNBC

Rebecca Dent, MD, discusses how investigators are targeting pathways in patients with triple negative breast cancer.

Rebecca Dent, MD, a senior consultant and head of Medical Oncology Department at the National Cancer Centre Singapore, discusses how investigators are targeting pathways in patients with triple negative breast cancer (TNBC).

Dent says that physicians in this setting having been trying to target the AKT pathway considering how important it is in carcinogenesis. PI3K and mTOR inhibition have been looked at previously, but she believes the importance of AKT inhibitors have been underappreciated, especially in the TNBC space.

Up to 40% of patients with TNBC have loss-of-function negative regulator and gain-of-function positive regulator aberrations in the AKT pathway, according to Dent. Some things can things can up-regulate AKT in a patient beyond their mutational status, such as the impact of chemotherapy. Preclinical data looking at cell lines in these patients showed that when investigators added AKT inhibitors for taxane-based chemotherapy, the benefits were not just additive, but synergistic, she thinks. This data was the basis for the randomized phase 2 LOTUS trial (NCT02162719) of paclitaxel versus ipatasertib (RG7440) in patients with metastatic TNBC.

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