Grant: Project Grant

Glioblastoma (GBM) is a highly malignant brain tumor where less than 5% of patients survive beyond five years. This dismal prognosis calls for fresh ideas and new treatment regimens. Recently, brain tumor initiating cells (BTICs), also called brain tumor stem cells, were discovered and they exploit the immune system (macrophages and microglia) by suppressing their activity or by eliciting growth factors to sustain brain tumor growth. An important and novel approach would thus be to rejuvenate or mobilize the compromised macrophages and microglia to contain BTICs. The collaboration between Drs. John Kelly (neurosurgeon/glioma biologist), Jeff Dunn (magnetic resonance imaging, MRI) and Wee Yong (neuroimmunologist) has uncovered generic medications with the capacity to stimulate macrophages/microglia. These include an anti-fungal medication, amphotericin B, and vitamin B3 (niacin). Amphotericin B is poorly tolerated in humans so the group has developed niacin further. Impressively, the group has found that in mice with brain tumors, treatment with niacin mobilizes the compromised immune cells, reduces tumor volume as detected through MRI and histology, and significantly prolongs the lifespan of mice. Remarkably, the life-extending impact of niacin exceeds that of the current front line therapy for GBM, temozolomide, and the combination of niacin and temozolomide has even better outcomes. To bring the laboratory findings to the clinic, the team now includes two neuro-oncologists, Paula de Robles and Gloria Urgoiti. Together, the team will determine how niacin stimulates immune cells to contain brain tumor growth, how best to further mobilize the activity of niacin, and conduct a Phase I/2 trial of niacin as an immune stimulator in GBM patients. Collectively, this team seeks to uncover new insights of GBM and translate therapeutics from the bench to bedside to mobilize the normally protective immune system to improve the prognosis of GBM.