Metformin enhances alpelisib sensitivity in HER2+ breast cancer by suppressing cancer stemness and oncogenic signaling.

ABSTRACT:

Introduction

Alpelisib, a selective PI3Kα inhibitor that targets PIK3CA mutations, is approved for hormone receptor-positive, HER2-negative breast cancer. However, its therapeutic potential in HER2-positive disease remains underexplored. Hyperglycemia, a frequent adverse event of alpelisib, limits its clinical application. Metformin, an antidiabetic drug with reported anticancer activity, may counteract alpelisib-induced hyperglycemia while enhancing its antitumor efficacy.

Methods

We evaluated the effects of alpelisib alone and in combination with metformin in HER2-overexpressing breast cancer cell lines SK-BR-3 and BT-474. Cell viability, colony formation, and tumorsphere assays were performed to assess proliferation and stemness. Flow cytometry was used to analyze ALDH1-p

SUBMITTER: Shi Y 

PROVIDER: S-EPMC12672257 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature