Brain Cancer Research in the Genomics Era
UAB a Participant in Ivy Genomics-Based Medicine Project
Cancer genomics and high-throughput computing make it feasible to map genetic differences in tumors that may lead to more effective and individualized patient treatment. The Ben and Catherine Ivy Foundation has selected UAB to participate in the Ivy Genomics-Based Medicine Project, a national consortium of cutting-edge hospitals and research centers. The group strives to tailor drug therapies to specific mutational characteristics of brain gliomas.
Malignant gliomas are the most frequent primary brain tumors in adults, accounting for half of the 17,000 brain tumors diagnosed in the United States each year. Prognosis is bleak: about half of patients live 1 year after diagnosis.
The Ben and Catherine Ivy Foundation is the nation’s largest privately funded foundation dedicated to improving survival and quality of life for brain tumor patients. “The speed and efficiency of the Ivy Foundation’s efforts in translational research potentially will make a significant difference in how we treat gliomas,” says UAB neurobiologist G. Yancey Gillespie, PhD, principal investigator for the UAB arm of the project.
Currently all brain cancer patients receive similar treatment, but investigators hypothesize that genetic differences in individual tumors could potentially help predict the best treatment choice. Once researchers pinpoint which genetic mutation responds to which regimen, they can tailor treatment to each tumor’s genetic profile. For example, it appears that certain genomic mutations may allow for better results with the oncolytic virus and antiangiogenic therapies currently being studied in various trials at UAB.
Identifying Candidate Drugs
“Pharmaceutical companies and laboratories have developed a raft of new drugs, but we don’t have a rapid, efficient way to assess their potential,” Gillespie says. Genetically engineered animal models based on older tumor cell lines have limited predictive capacity, he says. Tumors generated from these cell lines do not closely resemble human tumors, but advances in animal model engineering now permit development of gliomas with some human disease features.
“We are testing drugs in tumors established from patients’ tissue and introduced directly into animal models. We now have 60 or 70 of these more predictive genetic models available,” he says. Researchers plan to test 20 drugs, in several dilutions, in at least 40 different biological models. This enormaous undertaking is only possible by combining the resources of the nine participating institutions.
The Ivy Foundation charged the Translation Genomics Research Institute (TGen) to coordinate and manage the 5-year project. During the initial 18-month phase, UAB and other laboratories are screening dozens of anticancer drugs for tumor-fighting response in the genetic model systems. TGen will perform before and after genomic analyses of the tumors to determine how the pathways are affected. Real-time collaborative linkage facilitates comparison of results across institutions on a diverse set of tumors and treatment response patterns.
A clinical trial for patients with recurrent glioblastoma multiforme is the project’s second phase. “This new paradigm for drug testing may translate drug therapies to clinical treatment with unheard-of efficiency,” Gillespie says.
Ivy Genomics Medicine-Based Project
Henry Ford Hospital, Detroit
Mayo Clinic, Rochester
The Ohio State University, Columbus
The University of Texas M.D. Anderson Cancer Center, Houston
University of California, San Franscisco
Case Western Reserve University, Cleveland
Van Andel Research Institute, Grand Rapids
Translational Genomics Research Institute, Phoenix
University of Alabama at Birmingham
FOR MORE INFORMATION
Dr. Yancey Gillespie
Dr. James Markert
1.800.UAB.MIST
mist@uabmc.edu