Targeting and Therapeutic Monitoring of H3K27M-Mutant Glioma

Kyle Wierzbicki, Karthik Ravi, Andrea Franson, Amy Bruzek, Evan Cantor, Micah Harris, Morgan J Homan, Bernard L Marini, Abed Rahman Kawakibi, Ramya Ravindran, Rodrigo Teodoro, Viveka Nand Yadav, Carl Koschmann
Current Oncology Reports 2020 February 6, 22 (2): 19

PURPOSE OF REVIEW: H3K27M is a frequent histone mutation within diffuse midline gliomas and is associated with a dismal prognosis, so much so that the 2016 CNS WHO classification system created a specific category of "Diffuse Midline Glioma, H3K27M-mutant". Here we outline the latest pre-clinical data and ongoing current clinical trials that target H3K27M, as well as explore diagnosis and treatment monitoring by serial liquid biopsy.

RECENT FINDINGS: Multiple epigenetic compounds have demonstrated efficacy and on-target effects in pre-clinical models. The imipridone ONC201 and the IDO1 inhibitor indoximod have demonstrated early clinical activity against H3K27M-mutant gliomas. Liquid biopsy of cerebrospinal fluid has shown promise for clinical use in H3K27M-mutant tumors for diagnosis and monitoring treatment response. While H3K27M has elicited a widespread platform of pre-clinical therapies with promise, much progress still needs to be made to improve outcomes for diffuse midline glioma patients. We present current treatment and monitoring techniques as well as novel approaches in identifying and targeting H3K27M-mutant gliomas.

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