Co-targeting HSP90 alpha and CDK7 overcomes resistance against HSP90 inhibitors in BCR-ABL1+ leukemia cells

ABSTRACT: HSP90 inhibitors (HSP90i) have not entered routinely in the clinics, primarily due to the associated resistance via heat shock response (HSR) induction and dose limiting toxicity. In this study, we employed genetic KO and knockdown (KD) models of HSP90 isoforms (α and β) for extensive multi-omics-based in vitro and in vivo characterization and identified HSP90α as the primary driver of malignancy of the two isoforms in BCR-ABL1+ leukemia cells. Notably, combinatorial ex vivo drug sensitivity screenings identified CDK7 inhibitors (CDK7i) as drugs synergizing with HSP90α inhibition.

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture, Lymphoblast

DISEASE(S): Chronic Myelogenous Leukemia

SUBMITTER: Thomas Lenz  

LAB HEAD: Kai Stühler

PROVIDER: PXD041871 | Pride | 2024-01-26

REPOSITORIES: Pride