Fighting glioblastoma (GBM) – a common form of brain tumor – is a challenging task. Despite years of study, current treatments have failed to extend the survival of patients beyond 15 months.
But Madan Kwatra, PhD, is hoping to add a new weapon to the therapeutic arsenal.
Through a grant from the National Center for the Advancement of Translational Science (NCATS), Kwatra is collaborating with the pharmaceutical company AztraZeneca to conduct pre-clinical studies to determine if a drug originally designed to fight lung cancer can disrupt glioblastoma tumor growth in the brain.
“Glioblastoma is a beast of a cancer and thus far no therapies seem to work,” says Kwatra, an associate professor in Duke’s Department of Anesthesiology and a member of the Duke Cancer Institute since 1989. “Finding a therapy to beat it would be like a moon landing for us – really big!”
The NCATS grant is one of four the National Institutes of Health awarded in July 2015 as part of its New Therapeutic Uses program. The program links academic research groups with pharmaceutical industries to explore how scientists might repurpose drugs designed for one disease to defeat different disorders.
Kwatra’s excitement stems from recent discoveries that a subset of GBM tumors show elevated activity of epidermal growth factor receptor (EGFR) -- a protein that affects tumor growth. Tumors with overactive EGFR also have enhanced activity of another protein called HER2.
Coincidentally, AztraZeneca has a drug compound, called AZD9291, that inhibits both.
“No drug companies are developing new drugs for glioblastoma, so when I saw on the NCATS website that AstraZeneca had this compound, I got really excited,” Kwatra says.
Kwatra believes that AZD9291 will be more effective than any previously tested EGFR kinase inhibitor for glioblastoma because AZD9291 efficiently crosses the blood-brain barrier – an insurmountable challenge to many other drugs.
Over the next ten months, Kwatra’s collaboration with AztraZeneca will allow his team to test the AZD9291 compound in a large collection of pre-clinical models of GBM tumors whose molecular profiles are well known. By determining which tumors respond – and which don’t – he hopes to create guidelines for truly personalized medicine for patients suffering from glioblastoma.
“If this works, we could move to phase 1b trial in less than a year and complete a randomized phase II trial within three years,” Kwatra says. “With a disease where we currently tell people they may die within 15 months, we need that kind of urgency.”
The “Evaluation of AZD9291 in Glioblastoma Patients with Activated EGFR” study is funded by NCATS through grant number 1-UH2-TR001370-01. The academic partners are Madan M. Kwatra, Ph.D., and Glenn J. Lesser, MD. The Industry Partner is AstraZeneca. More information available at http://www.ncats.nih.gov/news/releases/2015/ntu-awards