The following is a summary of “CDKN2A deletion remodels lipid metabolism to prime glioblastoma for ferroptosis,” published in the June 2023 issue of the Cancer Cell by Minami et al.
Heterogeneous metabolic reprogramming in malignant tumors impedes the identification of translatable vulnerabilities for metabolism-targeted therapy. It remains unclear how molecular alterations in malignancies promote metabolic diversity and distinct targetable dependencies.
Researchers compile lipidomic, transcriptomic, and genomic data from 156 molecularly distinct glioblastomas (GBM) tumors and their derivative models. Through an integrated analysis of the GBM lipidome and molecular datasets, they identify that CDKN2A deletion modifies the GBM lipidome, notably redistributing oxidizable polyunsaturated fatty acids into distinct lipid compartments.
Therefore, CDKN2A-deleted GBMs exhibit more significant lipid peroxidation, thereby priming tumors selectively for ferroptosis. This study provides a molecular and lipidomic resource of clinical and preclinical GBM specimens, which they use to identify a therapeutically exploitable association between a recurrent molecular lesion and altered lipid metabolism in GBM.
Source: sciencedirect.com/science/article/pii/S153561082300168X