Induction of Triple-Negative Breast Cancer Cell Death and Chemosensitivity Using mTORC2-Directed RNAi Nanomedicine.

ABSTRACT:

Abstract

Alterations in the PI3K/mTOR signaling pathway are often seen in triple-negative breast cancers (TNBC), a breast cancer subtype characterized by limited molecularly targeted treatment options and poorer patient outcomes. We report that gene amplification or overexpression of the mTORC2-required cofactor RICTOR correlated with increased mTORC2 signaling and worse patient outcomes in clinical breast cancer expression datasets, supporting studies examining selective mTORC2 inhibition in TNBC. The mTOR kinase inhibitor PP242 blocks both mTORC1 and mTORC2, which decreases growth and survival of RICTOR-amplified TNBC cells. However, mTORC1 inhibition by PP242 causes resurgent PI3K signaling, limiting its therapeutic impact. In contrast, knockdown using siRNA designed against Ric

SUBMITTER: Patel SS 

PROVIDER: S-EPMC11921867 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature