Major Grant Advances Personalized Therapy for Brain Tumors
Researchers at The University of Texas M. D. Anderson Cancer Center will advance two new therapeutic approaches for malignant brain tumors and develop biomarkers to guide treatment decisions under a major translational research grant from the National Cancer Institute.
The Specialized Program of Research Excellence (SPORE) grant for brain tumor research is the 11th such grant received by M. D. Anderson under the NCI's program, which is designed to move basic science findings into early stage clinical trials.
M. D. Anderson already holds SPORE grants in leukemia and melanoma as well as cancers of the breast, bladder, pancreas, ovaries, uterus, head and neck, prostate and lung, with the last shared with The University of Texas Southwestern Medical Center in Dallas. The 11 grants out of 60-plus SPOREs awarded by the NCI are the most held by a single institution.
"This award marks a very significant event for M. D. Anderson and indicates the important role that the institution plays in the field of translational research," said Raymond DuBois, M.D., Ph.D, M. D. Anderson provost and executive vice president. "We are essentially leading the way in developing multidisciplinary research teams to accelerate the transition of basic knowledge into the clinic. I am extremely proud of our neuro-oncology team and all of the people involved who will use this brain tumor SPORE to ultimately make a difference for patients."
The five-year, $12.5 million brain tumor SPORE builds on existing institutional expertise in multiple departments, said W. K. Alfred Yung, M.D., chair of M. D. Anderson's Department of Neuro-Oncology and co-principal investigator of the brain tumor SPORE with Oliver Bogler, Ph.D., associate professor in M. D. Anderson's Department of Neurosurgery.
"All four of the projects funded by this grant apply molecular and genetic approaches to develop new targeted therapies and biomarkers that will improve treatment by personalizing therapy," Yung said.
The NCI estimates that 21,810 new cases of brain or central nervous system tumors will be diagnosed in 2008, and about 13,000 people will die from brain malignancies. Tumors range in severity from benign to the highly malignant glioblastoma multiforme, which will be the focus of M. D. Anderson's SPORE.
Project 1: Deploying a tumor-killing virus
The engineered adenovirus Delta-24-RGD, developed at M. D. Anderson, will advance to clinical trial and a second-generation version will be developed as a single therapy and in combination with other drugs. Delta-24 will be injected directly into tumors during a phase I clinical trial that is under review at the U.S. Food and Drug Administration. The virus is genetically altered to prevent it from entering normal cells but attacks glioblastoma cells, which lack a specific anti-viral protein. Principal investigators are Juan Fueyo, M.D., associate professor of neuro-oncology, and Frederick Lang, M.D., professor of neurosurgery.
Project 2: Blocking a malignant pathway
Drugs that block a molecular signaling cascade known to fuel brain tumors - the PI3K pathway - will be developed and tested in phase I trials. Both individual targeted molecules and rational drug combinations will be studied for their potential to inhibit PI3K. One candidate inhibitor has been developed by Garth Powis, Ph.D., professor and chair of M. D. Anderson's Department of Experimental Therapeutics, who is co-PI with Yung and Bogler on the project.
Project 3: Identifying treatment guideposts
Researchers are developing and validating a set of genes that predict survival and sensitivity to treatment for glioblastoma patients. This biomarker approach to sorting out personalized treatment is being conducted in collaboration with existing clinical trials testing a variety of therapies and combinations for glioblastoma. Co-principal investigators are Kenneth Aldape, M.D., professor in the Department of Pathology, and Howard Colman, M.D., Ph.D., assistant professor of neuro-oncology.
Project 4: Pinpointing genetic role in brain impairment
By analyzing the genetic makeup of glioblastoma patients and relating it to the type and degree of cognitive impairment they experience after radiation treatment, researchers aim to identify and understand genes that affect cognitive outcomes. Co-principal investigators are Melissa Bondy, Ph.D., professor in the Department of Epidemiology, and Christina Meyers, Ph.D., professor of neuro-oncology.
The four research projects are supported by five cores: administrative (Yung and Bogler); pathology (Aldape and colleague Craig Fuller, M.D., Ph.D., professor of pathology); clinical (Mark Gilbert, M.D. professor of neuro-oncology); biostatistics (Kenneth Hess, Ph.D., associate professor in the Department of Biostatistics); and animal models (Charles Conrad, M.D., associate professor of neuro-oncology). 06/25/08