Purine salvage promotes treatment resistance in H3K27M-mutant diffuse midline glioma.
Erik R PetersonPeter SajjakulnukitAndrew J ScottCaleb HeaslipAnthony AndrenKari Wilder-RomansWeihua ZhouSravya PalavalasaNavyateja KorimerlaAngelica LinAlexandra O'BrienAyesha KothariZitong ZhaoLi ZhangMeredith A MorganSriram VennetiCarl KoschmannNada JabadoCostas A LyssiotisMaria G CastroDaniel R WahlPublished in: Cancer & metabolism (2024)
Our results indicate that DMG-H3K27M cells rely on highly active purine synthesis, both from the de novo and salvage synthesis pathways. However, highly active salvage of free purine bases into mature guanylates can bypass inhibition of the de novo synthetic pathway. We conclude that inhibiting purine salvage may be a promising strategy to overcome treatment resistance in DMG-H3K27M tumors.