Clinical efficacy of ONC201 in H3K27M-mutant diffuse midline gliomas is driven by disruption of integrated metabolic and epigenetic pathways
Venneti S, Kawakibi AR, Ji S, Waszak SM, Sweha SR, Mota M, …, Cartaxo RT, John V, Messinger D, …, Gardner SL, Koschmann C (84 authors).
Cancer Discovery, Nov 2023, Vol 13(11), pp 2370-2393. doi:10.1158/2159-8290.CD-23-0131
In plain English
A drug called ONC201 helps some children with an aggressive, hard-to-treat brain tumor. This study worked out how it helps — by simultaneously cutting off the tumor's energy supply and flipping the chemical switches that keep its cancer genes turned on.
For scientists
H3K27M-mutant diffuse midline glioma (DMG) patients have no proven effective therapies. ONC201 is an imipridone compound with clinical activity in H3K27M-mutant DMG. This study investigates the integrated metabolic and epigenetic mechanisms underlying ONC201's clinical efficacy in this devastating pediatric brain cancer.