TGen to lead multidisciplinary search for new drugs that could help treat GBM

The Translational Genomics Research Institute (TGen) will lead a multidisciplinary search for new drugs that could help treat the most common and lethal form of brain cancer.

A $4.5 million grant from the National Institutes of Health (NIH) will fund the search to find new ways of treating glioblastoma multiforme (GBM), the most common type of primary brain tumors. Primary brain tumors are among the top 10 causes of cancer death in the U.S., and more than 80,000 Americans have primary malignant brain tumors.

Collaborating with TGen on this 5-year study are the Sanford-Burnham Medical Research Institute (Sanford-Burnham); Van Andel Research Institute (VARI); the Intellectual Property & Science division of Thomson Reuters; and the NIH's National Cancer Institute (NCI).

"The exceptional team assembled for this study will mine vast amounts of data to come up with possible cancer vulnerabilities and the most promising ways to attack GBM, giving new hope to brain-tumor patients," said Dr. Michael Berens, Ph.D., Director of TGen's Cancer and Cell Biology Division, and principal investigator of the project.

GBM grows rapidly and commonly spreads to nearby brain tissue. It usually is treated by surgical removal of as much of the tumor as possible, followed by radiation and conventional chemotherapy. The prognosis is very poor, and patients survive a median of only 14 months after diagnosis.

The goal of this study is to use newly uncovered knowledge about the genomes of hundreds of glioblastoma specimens to discover new medicines that can precisely target tumors, shrinking or even eliminating them, with minimal harm to other cells and minimal side effects for patients.

In a discovery phase, TGen, VARI and Thomson Reuters will conduct the most extensive scan ever undertaken of available public data about the potential genetic causes of GBM. This search will identify the most promising genes and cellular pathways to target. These targets will be referenced against a database of 54 patient tumor models, looking for small molecules that could lead the way to new cancer drugs.

The resulting pre-clinical drug-treatment models will be tested and validated by Sanford-Burnham, creating the best available data to share with the general scientific community, including pharmaceutical companies.

"We hope to put the scientific and technical competency of chemical biology at Sanford-Burnham to work in this study, helping to generate prototypes of new medicines that could eventually be delivered to patients who desperately need them," said Dr. Kristiina Vuori, M.D., Ph.D., Sanford-Burnham's President and Director of its NCI-designated Cancer Center.

In addition, the study team will meet monthly with the NCI's Cancer Target Discovery and Development (CTDD) Network, sharing best practices that will help other researchers avoid duplication and pursue the most promising lines of investigation. The CTDD Network goal is to bridge the gap between the enormous volumes of genomic data generated by the comprehensive molecular characterization of various cancer types and the ability to use these data for the development of human cancer therapeutics.

"The computational tools we have developed to enable personalized medicine will comb through extensive data sets, looking to systematically identify novel drug targets and match the best available therapies with patients' individual tumors," said Dr. Craig Webb, Ph.D., Head of VARI's Laboratory of Translational Medicine, which brings to the study expertise in bioinformatics and personalized medicine. "Working closely with the CTDD Network will ensure that our ongoing research remains cutting-edge."

In addition to the team led by TGen, the CTDD Network consists of: Columbia University, Emory University, the Dana-Farber Cancer Institute, University of California San Francisco, University of Texas MD Anderson Cancer Center, Cold Spring Harbor Laboratory, University of Texas Southwestern Medical Center, and the Broad Institute.

The MetaCore and MetaMiner (oncology) offerings from Thomson Reuters provide some of the world's best applications for systems biology in the analysis of cellular pathways, the cascade of chemical events that take place within the lifecycles of normal and cancerous cells.

"Our unique biological systems technology enables complete reconstruction of mammalian cellular functionality, providing precise tumor analysis and accelerating target discovery," said Dr. Yuri Nikolsky, Ph.D., Vice President of Research & Development at Thomson Reuters.

The study, formally titled "Systematic Development of Novel, Druggable Cancer Targets," will build on information from The Cancer Genome Atlas (TCGA), an NCI project. TCGA is assembling vast bodies of information about how errors in DNA cause cells to grow uncontrolled, causing cancer. The TCGA is focused on several types of cancer, including GBM.

"The study's combination of bioinformatics and experimental approaches is innovative, and should enable development of novel molecular targets not only in GBM, but also in multiple cancer types," TGen's Dr. Berens said.