Study of “Exceptional Responders” Among Glioblastoma Patients Treated with Chemotherapy Leads to ID of New Drug Target (PI3Kγ) for Deadly Brain Cancer; In Animal Models, Treatment with PI3Kγ Inhibitors Resulted in Durable Responses to Chemotherapy

Despite access to some of the best possible medical care in the world, US Senators John McCain and Edward Kennedy both died within 18 months of their diagnosis of glioblastoma, an aggressive form of brain cancer. While this deadly outcome typifies the nature of this disease, some glioblastoma patients see exceptional benefits from chemotherapy and survive beyond expectations. Why this happens has been revealed by researchers at the University of Minnesota in a new study published online on April 20, 2021in PNAS. The article is titled “PI3Kγ Inhibition Suppresses Microglia/TAM Accumulation in Glioblastoma Microenvironment to Promote Exceptional Temozolomide Response” ( "Deciphering the molecular underpinning of these exceptional responses may hold the key to transforming the hope for miracles into the reality of an expected cure for glioblastoma patients," said Clark C. Chen (, MD, PhD, Lyle French Chair in Neurosurgery and Head of the Department of Neurosurgery at the University of Minnesota Medical School, who is senior author of the study. The study team looked at the gene expression profiles of glioblastoma specimens collected from approximately 900 glioblastoma patients from regions across the world to identify unique features associated with exceptional responders, defined as glioblastoma patients who survive more than two years after treatment. "We utilized different state-of-the-art analytics to study these samples, including methods innovated by Dr. Aaron Sarver, a member of the University of Minnesota (U of M) Institute of Health Informatics. Impressively, these analytics converged on a single observation, a paucity of microglia and macrophages," Dr. Chen said.
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