Targeting PI3K inhibitor resistance in breast cancer with metabolic drugs.

ABSTRACT: Activating PIK3CA mutations, present in up to 40% of hormone receptor-positive (HR⁺), human epidermal growth factor receptor 2-negative (Her2^-) breast cancer (BC) patients, can be effectively targeted with the alpha isoform-specific PI3K inhibitor Alpelisib. This treatment significantly improves outcomes for HR⁺, Her2^-, and PIK3CA-mutated metastatic BC patients. However, acquired resistance, often due to aberrant activation of the mTOR complex 1 (mTORC1) pathway, remains a significant clinical challenge. Our study, using in vitro and orthotopic xenograft mouse models, demonstrates that constitutively active mTORC1 signaling renders PI3K inhibitor-resistant BC exquisitely sensitive to various drugs targeting cancer metabolism. Mechanistically, mTO

SUBMITTER: Gremke N 

PROVIDER: S-EPMC11926384 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature