Wild-type isocitrate dehydrogenase under the spotlight in glioblastoma

Gabriel Alzial (1) , Ophelie Renoult (1) , François Paris (1, 2) , Catherine Gratas (1, 3) , Anne Clavreul (4, 3) , Claire Pecqueur (1)

1 CRCINA-ÉQUIPE 14 - Endothelium Radiobiology and Targeting
2 UNICANCER/ICO - Institut de Cancérologie de l'Ouest [Angers/Nantes]
3 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
4 CRCINA-ÉQUIPE 17 - Design and Application of Innovative Local Treatments in Glioblastoma

Brain tumors actively reprogram their cellular metabolism to survive and proliferate, thus offering potential therapeutic opportunities. Over the past decade, extensive research has been done on mutant IDH enzymes as markers of good prognosis in glioblastoma, a highly aggressive brain tumor in adults with dismal prognosis. Yet, 95% of glioblastoma are IDH wild-type. Here, we review current knowledge about IDH wild-type enzymes and their putative role in mechanisms driving tumor progression. After a brief overview on tumor metabolic adaptation, we present the diverse metabolic function of IDH enzymes and their roles in glioblastoma initiation, progression and response to treatments. Finally, we will discuss wild-type IDH targeting in primary glioblastoma.

Domaines: Cancer

Gabriel Alzial, Ophelie Renoult, François Paris, Catherine Gratas, Anne Clavreul, et al.. Wild-type isocitrate dehydrogenase under the spotlight in glioblastoma. Oncogene, 2021, Online ahead of print. ⟨10.1038/s41388-021-02056-1⟩. ⟨inserm-03434277⟩