Depleting the Action of EZH2 through PI3K-mTOR Inhibition to Overcome Metastasis and Immunotherapy Resistance in Triple-Negative Breast Cancer.

ABSTRACT: Almost half of patients with triple-negative breast cancer develop distant metastases, heralding unfavorable outcomes. Here, we provide novel insights into the contribution of the PI3K-mTOR pathway to the triple-negative breast cancer phenotypes that promote growth, migration, metastasis, and therapy resistance. Specifically, we demonstrate that dual targeting of PI3K and mTOR but not PI3K alone inhibits cancer cell proliferation and migration in vitro. Dual PI3K-mTOR inhibition with paxalisib not only promotes a favorable mesenchymal-to-epithelial phenotype but also inhibits signatures associated with metastasis-initiating cells, including the highly aggressive cancer stem cell phenotype, persister cancer cell phenotype (p65, FOXQ1, NRF2, and NNMT), and a cancer drug resistance signature

SUBMITTER: Melino M 

PROVIDER: S-EPMC12485387 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature