Wild-type isocitrate dehydrogenase under the spotlight 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.

Automated summary

Research has focused on mutant IDH enzymes as prognostic markers in glioblastoma, but the majority of cases are IDH wild-type. This review explores the current understanding of wild-type IDH enzymes and their role in tumor progression, as well as discussing potential targeting strategies in primary glioblastoma.