Purine metabolism promotes radioresistance and is a therapeutic target in glioblastoma.

Profound intratumoral genomic heterogeneity has limited the ability of targeted therapies to overcome therapy resistance in glioblastoma. We have defined purine metabolism as a key mediator of DNA repair and radiation resistance in glioblastoma. Because many glioblastoma oncogenic drivers activate purine metabolism, its inhibition may overcome therapy resistance despite intratumoral genomic heterogeneity.