Recurrent GBM Brain Tumors with Few Mutations Respond Best to Immunotherapy
Glioblastoma brain tumors, known for their lethality, occasionally respond to new immunotherapies upon recurrence, allowing up to 20% of patients to surpass expected survival times. The quest to understand this phenomenon has been a focal point for researchers aiming to leverage immunotherapies to save more lives.
A groundbreaking discovery by a team from the Preston Robert Tisch Brain Tumor Center at Duke University sheds light on this issue. They found that recurrent glioblastoma tumors with very few mutations are significantly more vulnerable to immunotherapies compared to those with a high number of mutations. This insight, published on January 13, 2021, in Nature Communications, could serve as a predictive biomarker to help clinicians identify which tumors are most likely to respond to immunotherapy, potentially leading to more effective treatment strategies.
David Ashley, MD, PhD, a professor in the Department of Neurosurgery and the study's senior author, expressed the challenges faced in treating glioblastoma, stating, "It’s been frustrating that glioblastoma is incurable and we’ve had limited progress improving survival despite many promising approaches." He highlighted the success seen with various immunotherapies, including the poliovirus therapy developed at Duke, but noted that about 80% of patients still succumb to the disease.
The research involved genomic analyses of recurrent glioblastoma tumors from patients treated with Duke’s poliovirus therapy and those who received checkpoint inhibitors, a therapy that unleashes the immune system to attack tumors. Patients with recurrent glioblastomas and fewer tumor mutations survived longer than those with highly mutated tumors, a finding exclusive to patients with recurrent tumors and not applicable to newly diagnosed, untreated patients.
This discovery not only offers hope for more targeted and effective immunotherapies but also underscores the importance of genetic analysis in understanding and treating complex cancers like glioblastoma.