Updates in IDH-Wildtype Glioblastoma

Abstract

Glioblastoma is the most aggressive primary brain tumor with a poor prognosis. The 2021 WHO CNS5 classification has further stressed the importance of molecular signatures in diagnosis although therapeutic breakthroughs are still lacking. In this review article, updates on the current and novel therapies in IDH-wildtype GBM will be discussed.

Keywords: Clinical trials; Glioblastoma; IDH-wildtype; Precision medicine; Targeted therapy.

Fig. 1

A 70-year-old woman who presented with headache and behavioral changes and was found to have an IDH-wildtype GBM over the left frontal region causing minimal mass effect. Contrast-enhanced T1 image shows a large necrotic mass over the left frontal region with irregular thick rind (A). Elevated CBV on MR perfusion correlates to areas of enhancement (B). Compared to DWI map (C), cellular heterogeneity is evident within the tumor fields as more hypercellular areas demonstrates higher signal drop on ADC map (D)

Fig. 2

Proposed molecular testing algorithm for HGG. *Consider testing in young adults. Abbreviations: HGG, high-grade gliomas; IDH, isocitrate dehydrogenase; FISH, fluorescence in situ hybridization; SNP, single nucleotide polymorphism; WHO, World Health Organization; DMG, diffuse midline glioma; EGFR, epidermal growth factor receptor; RNA, ribonucleic acid; EZHIP, EZH Inhibitory Protein; MMR, mismatch repair; cMMRD, constitutional mismatch repair deficiency; BRAF, B-Raf; MYCN, N-myc proto oncogene; RTK, receptor tyrosine kinase; NTRK, neurotrophic tyrosine receptor kinase; TERT, telomerase reverse transcriptase