DUARTE, Calif., October 18, 2011 — The National Cancer Institute has awarded City of Hope a five-year, $1.2 million grant to investigate and develop a cancer treatment that targets a cellular pathway associated with both brain tumors and diabetes complications. Behnam Badie, M.D., chief of the Division of Neurosurgery and director of the Brain Tumor Program, is principal investigator on the grant, which supports research into turning the body’s own defenses against brain cancers such as glioma.
“Current treatment options for brain tumors can be limited due to the sensitive location of the cancer and the body’s natural protective barriers,” Badie said. “My team’s research has focused on using the immune system to fight cancers, and one of the ways we are trying to do that is by investigating an inflammatory process most often associated with diabetes.”
In people with diabetes, too much sugar circulates in the blood, and harmful substances called advanced glycation end products (AGEs) form when this excess sugar binds to molecules in the body. AGEs can then activate what are called receptors for advance glycation end products, or RAGE.
Activating RAGE can kick-start inflammation, part of the immune system’s response to infections, damage or injury. It is a natural process that can lead to healing. In patients with diabetes, however, chronic inflammation can lead to deadening of nerve sensation, vision loss and congestive heart failure.
Badie recognized similar biochemical activity in brain tumors and suspected that RAGE activation in brain tumors might also activate immune cells known as macrophages, which seek to attack and destroy damaged or faulty cells, like cancer cells.
He found that brain tumors use RAGE activation in an opposite manner than diabetes, to shut down macrophages. The research team suspects the cancer cells may do this through a protein called SB100B. Gliomas (and melanomas) express high levels of SB100B, a protein that interacts with RAGE.
“The grant will enable us to further our understanding of RAGE activation in gliomas and melanomas,” Badie said, “and help identify drug targets that can block RAGE and activate the immune response to the cancer cells.”
Badie is collaborating with City of Hope colleagues Rama Natarajan, Ph.D., National Office Products Industry Professor in Diabetes Research; Jana Portnow, M.D., assistant professor in the Department of Medical Oncology & Therapeutics Research; and Christine Brown, Ph.D., assistant research professor in the Department of Cancer Immunotherapeutics and Tumor Immunology. Their research seeks a way to stop glioma’s chemical blockade and restart RAGE activation of the macrophages.