Targeting mTORC1 to promote ferroptosis and apoptosis in endometrial cancer with PI3K-Akt-mTOR pathway mutation.

ABSTRACT:

Aims

Endometrial cancer (EC) is often driven by hyperactivation of the PI3K-Akt-mTOR (PAM) pathway due to mutations in PTEN and/or PI3K genes. While mechanistic target of rapamycin complex 1 (mTORC1) inhibitors show limited efficacy as single agents in EC, previous studies suggest that they may sensitize the PAM-mutant cancer cells to ferroptosis, a regulated form of necrosis dependent on iron-catalyzed lipid peroxidation. We investigated whether combining mTORC1 inhibition with ferroptosis induction could overcome resistance mechanisms and improve therapeutic outcomes in EC.

Methods

We evaluated the effect of catalytic, allosteric, and bi-steric mTORC1 inhibition on ferroptosis sensitivity in EC cell lines with different PAM pathway mutational statuses. In vivo effic

SUBMITTER: Hu Y 

PROVIDER: S-EPMC12742288 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature