Defeat GBM Research Collaborative

Investigator Teams & Goals

Through research collaboration, four synergistic research cores focused on discovery, drug development, predictive biomarkers, and innovative clinical trials have been combined and are being driven by world-class teams with proven track records of research accomplishments to accelerate the pace of therapeutic discovery and improve patient survival.

By design, the individual project cores within the overall Defeat GBM initiative provide strategic data-sharing opportunities to inform the overall effort, and advance potential therapies through the drug discovery development process much more quickly. A prototype for precision medicine, Defeat GBM identifies the right biological targets, with the right therapies, for the right patients.

Core 1: Target Discovery

Led by Frank Furnari, PhD, Ludwig Institute for Cancer Research, University of California, San Diego

• The goal is to identify the right treatment target(s) and understand any associated resistance mechanisms (i.e. how the tumors escape or resist treatment).
• Molecular targets identified and prioritized here will then be advanced to each of the other three cores to develop therapeutic agents that not only inhibit the targets but also overcome drug resistance in GBM.

Core 2: Drug Development

Led by John de Groot, MD, University of Texas, MD Anderson Cancer Center and Ingo Mellinghoff, MD, Memorial Sloan Kettering Cancer Center

• The goal is to accelerate drug development by identifying existing molecules/drugs that can be applied specifically to GBM, both on their own and in rational combination, as well as develop novel drugs (at MD Anderson) specifically for GBM.
• The work of this core will also include research to better understand the molecular and biological response to clinical inhibitors at the “systems biology” level to develop rational combination therapies.
• Simultaneous investigation in the other research cores will aid the team in creating and matching drugs with the right patients depending on the molecular profile of the patient’s tumor.

Core 3: Predictive Markers (Biomarkers)

Led by Paul Mischel, MD, Ludwig Institute for Cancer Research, University of California, San Diego and Tim Cloughesy, MD, University of California Oncology Center, Los Angeles

• The goal is to identify and develop predictive biomarker panels to guide therapy — including combination therapy — for each patient based on the molecular composition of their tumor.
• These discoveries will then be used to better inform the simultaneous drug discovery in Core 2 above — as any markers that are identified as predicting response and/or resistance will be screened by the MD Anderson team for drugs or rational combinations of drugs.
• The identification of molecular biomarkers which predict drug response as well as those that will predict resistance to targeted therapy will help guide a more successful and rational treatment strategy for GBM patients.

Core 4: Innovative, Adaptive Clinical Trials

Principal investigators include Tim Cloughesy, MD, University of California Oncology Center, Los Angeles, Ingo Mellinghoff, MD, Memorial Sloan Kettering Cancer Center, and John de Groot, MD, University of Texas, MD Anderson Cancer Center

• The goal is to test novel targeted treatments in innovative clinical trials to validate molecular marker based personalized therapy for GBM.
• Advances in molecular biology and patient molecular profiling that may facilitate targeted therapy have provided a basis to improve clinical trial design. The Defeat collaborative is involved in an innovative public-private collaboration to implement a Global Adaptive Trial in GBM patients.
• An adaptive “biomarker enriched” clinical trial of targeted therapies for patients with GBM will seek to identify molecular sub‐groups of GBM patients that show the best responses to treatments targeting specific mechanisms. This novel trial design will improve the efficiency of early clinical testing and increase the probability of success in late phase registration trials seeking drug approval.