C-Terminal Hsp90 Inhibitors Overcome MEK and BRAF Inhibitor Resistance in Melanoma.

ABSTRACT: Targeted therapies for melanoma MEK and BRAF inhibitors fail due to the development of chemoresistance. As Hsp90 inhibitors target client proteins of resistant pathways, we hypothesised that C-terminal Hsp90 inhibitors will target BRAF/MEK inhibitor resistant melanoma cells by overcoming the resistant pathways. Two melanoma cell lines, A375 and A375 MEK/BRAF inhibitor resistant (A375MEKi) were utilised. The inhibitory concentrations (IC₅₀) of two C-terminal Hsp90 inhibitors, KU757 and KU758, were determined by CellTiter Glo. RNA sequencing was performed after treatment with KU757. Pathways targeted by differentially expressed genes were evaluated by David, IPA, GSEA, and by evaluating the cell cycle, apoptosis and oxidative phosphorylation. Expression levels of hub genes were ev

SUBMITTER: Subramanian C 

PROVIDER: S-EPMC11937850 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature