Enhancing cancer susceptibility to disulfidptosis by inducing cell cycle arrest and impairing DNA repair.

ABSTRACT: Disulfidptosis-a regulated cell death caused by disulfide stress under glucose starvation and high SLC7A11-offers a potential cancer vulnerability, but its regulatory landscape and therapeutic tractability remain unclear. We sought to (i) map disulfidptosis susceptibility across cancers, (ii) define associated pathways and regulators, and (iii) test whether targeting these pathways enhances disulfidptosis to improve antitumor efficacy. Methods: We curated 43 core regulators to compute the disulfidptosis score (D-score) across ~10,000 TCGA tumors, benchmarked with glucose-starvation datasets. Correlation screening yielded 506 candidate regulators, integrated into a refined score (D-score+). We associated D-score+ with hallmark pathways, genomic instability and DNA-repair signatures.

SUBMITTER: Lin J 

PROVIDER: S-EPMC12674887 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature