Kinomic profile in patient-derived glioma cells during hypoxia reveals c-MET-PI3K dependency for adaptation.

ABSTRACT: Hypoxic microenvironment is a hallmark of solid tumors, especially glioblastoma. The strong reliance of glioma-propagating cells (GPCs) on hypoxia-induced survival advantages is potentially exploitable for drug development. Methods: To identify key signaling pathways for hypoxia adaptation by patient-derived GPCs, we performed a kinase inhibitor profiling by screening 188 small molecule inhibitors against 130 different kinases in normoxia and hypoxia. Potential kinase candidates were prioritized for in vitro and in vivo investigations using a ranking algorithm that integrated information from the kinome connectivity network and estimated patients' survival based on expression status. Results: Hypoxic drug screen highlighted extensive modifications of kinomic lan

SUBMITTER: Cheng HS 

PROVIDER: S-EPMC8039937 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature