Purine Metabolism as a Therapeutic Target in Glioblastoma.

Abstract

The most frequent primary malignant brain tumor in adults is glioblastoma, and recurrence with subsequent mortality is a significant issue in nearly all patients. Glioblastoma features such as rapid proliferation, chemotherapy resistance, and plasticity rely on the maintenance of adequate nucleotide pools. In this review, we investigate the role of purine metabolism in glioblastoma biology. Purine pathways promote stemness and plasticity, increase stress adaptation, and shape tumor microenvironments. The main vulnerabilities causing these malignant phenotypes include de novo purine synthesis, guanine synthesis via inosine monophosphate dehydrogenase, synthetic lethality secondary to methylthioadenosine phosphorylase loss, and extracellular adenosine signaling.