Altered Metabolism and Treatment Resistance in Brain Cancer Patients

Daniel R Wahl
University of Michigan

Daniel Wahl, MD, PhD (Presenter) University of Michigan

Presenter Bio: Dr. Wahl is a physician scientist at the University of Michigan specializing in cancers of the central nervous system. His research focuses on the development of new treatment strategies for brain tumors and his laboratory group is especially interested in interactions between radiation and abnormal metabolism in glioblastoma. In the clinic, he cares for a wide variety of patients with both malignant and benign tumors of the central nervous system.

Relevant Financial Disclosures (within past 24 months, reported on May 07, 2026) Honorarium/Expenses Bruker Consultant Fees Admare Grant/Research Support Bruker Discussing Products? NO, presenter will NOT present educational content related to products/services of the ineligible company(ies) listed above. Conflict mitigation NOT REQUIRED.

Aggressive brain cancers like glioblastoma have a dismal prognosis and inevitably recur even after standard treatments like radiation. Altered metabolism is a hallmark of cancer, and our team has found that altered metabolism in brain cancer can cause treatment resistance. Indeed, we have found that numerous metabolites including purines and amino acids promote DNA repair and radiation resistance in glioblastoma. More recently, we have begun directly profiling metabolic activity in brain cancers using stable isotope tracing. In this procedure, we administer non-radioactive but heavy isotopically-labeled nutrients to brain tumor patients during their standard of care surgeries. By analyzing resected tumor and brain tissue by mass spectrometry, we have identified profound metabolic rewiring in adult brain cancer. While both brain cancers and non-cancerous cortex heavily take up glucose, they utilize it for different purposes. Cortex uses glucose to drive the TCA cycle and synthesize amino acids and neurotransmitters. Brain cancers downregulate these physiologic processes, take up amino acids from the environment, and utilize glucose-derived carbons for growth. This metabolic rewiring has therapeutic consequences, as targeting amino acid uptake or nucleotide synthesis are being explored for brain cancer patients through clinical trials. In addition to identifying novel therapeutic targets, direct profiling of cancer metabolism in patients could help predict which patients are most likely to respond to which metabolic therapy.