Integrated molecular and functional characterization of the intrinsic apoptotic machinery identifies therapeutic vulnerabilities in glioma.

ABSTRACT: Genomic profiling often fails to predict therapeutic outcomes in cancer. This failure is, in part, due to a myriad of genetic alterations and the plasticity of cancer signaling networks. Functional profiling, which ascertains signaling dynamics, is an alternative method to anticipate drug responses. It is unclear whether integrating genomic and functional features of solid tumours can provide unique insight into therapeutic vulnerabilities. We perform combined molecular and functional characterization, via BH3 profiling of the intrinsic apoptotic machinery, in glioma patient samples and derivative models. We identify that standard-of-care therapy rapidly rewires apoptotic signaling in a genotype-specific manner, revealing targetable apoptotic vulnerabilities in gliomas containing specific

SUBMITTER: Fernandez EG 

PROVIDER: S-EPMC11582606 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature