Inhibition of GPX4 induces the death of p53-mutant triple-negative breast cancer cells.

ABSTRACT:

Background

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high rates of tumor protein 53 (TP53) mutation and with limited targeted therapies. Despite being clinically advantageous, direct targeting of mutant TP53 has been challenging. Therefore, we hypothesized that p53-mutant TNBC cells rely upon other potentially targetable survival pathways.

Methods

In vitro and in silico screens were used to identify drugs that induced preferential death in TP53-mutant cells. The effect of the ferroptosis inducer ML-162 was tested both in vitro and in vivo and the mechanism of cell death following ML-162 treatment or GPX4 knockout was determined.

Results

High-throughput drug screening demonstrated that TP53-mutant TNBCs are highly s

SUBMITTER: Tahaney WM 

PROVIDER: S-EPMC12774971 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature