Phosphoproteomics identifies determinants of PAK inhibitor sensitivity in leukaemia cells.

ABSTRACT:

Background

The P21 activated kinases (PAK) are frequently dysregulated in cancer and have central roles in oncogenic signalling, prompting the development of PAK inhibitors (PAKi) as anticancer agents. However, such compounds have not reached clinical use because, at least partially, there is a limited mechanistic understanding of their mode of action. Here, we aimed to characterize functional and molecular responses to PAKi (PF-3758309, FRAX-486 and IPA-3) in multiple acute myeloid leukaemia (AML) models to gain insights on the biochemical pathways affected by these inhibitors in this disease and identify determinants of response in patient samples.

Methods

We mined phosphoproteomic datasets of primary AML, and used proteomics and phosphoproteomics to profile PAKi impact in

SUBMITTER: Casado P 

PROVIDER: S-EPMC11907924 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature