Integrative Multi-Omics Analyses Reveal Mechanisms of Resistance to Hsp90β-Selective Inhibition.

ABSTRACT:

Background/objectives

Targeting Hsp90β with isoform-selective inhibitors offers a promising therapeutic strategy with reduced toxicity compared to pan-Hsp90 inhibition. However, mechanisms of resistance to Hsp90β-selective inhibition remain poorly defined. This study aimed to identify molecular determinants of Hsp90β dependency and pharmacologic resistance across cancer types.

Methods

We integrated gene dependency, transcriptomic, proteomic, metabolomic, and drug sensitivity data from the Cancer Cell Line Encyclopedia with in vitro validation using the Hsp90β-selective inhibitor, NDNB-25. Comparative and correlation analyses were performed to identify resistance-associated pathways, followed by network and combination drug testing to validate functional interactions.

Resu

SUBMITTER: Mersich I 

PROVIDER: S-EPMC12608035 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature