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Defeat GBM Research Collaborative Progress Report: A Multitude of New Discoveries & A Push to Evaluate Potential New Drugs in Clinical Trials

National Brain Tumor Society shares updates on the portfolio of progress being made through its subsidiary, Cure GBM, LLC, and its flagship program, the Defeat GBM Research Collaborative


Today, we would like to provide a comprehensive update on the extensive discoveries and progress made thus far by our flagship research program, the Defeat GBM Research Collaborative (Defeat GBM).

Members of the Defeat GBM Research Collaborative at the 2016 NBTS Scientific Summit

NBTS launched Defeat GBM to connect a team of leading brain cancer experts through a collaborative infrastructure and utilize a multidisciplinary, team science approach to accelerate treatment development for patients with glioblastoma (GBM) – the most common, complex, treatment-resistant, and deadliest type of brain cancer. The idea was simple: change the way we fund and conduct GBM research, and change the calculus behind years of heartbreaking disappointments and achingly slow progress against these tumors.

With scientific endeavors and research efforts beginning in 2014, the overall goal of the Defeat GBM Research Collaborative is to catalyze the development of new treatments for glioblastoma (GBM) that will extend the lives of patients with this insidious cancer. Specifically, our aspiration is to double the percentage of GBM patients who survive five years or more beyond their initial diagnosis.

Operationally, we sought to do this by creating a research infrastructure that fosters teamwork and collaboration between many of the top minds in the field. Instead of funding rounds of individual grants to different researchers working alone on separate projects, we would establish and lead a large multi-institutional collaborative, capable of tackling many of the aspects involved in converting basic research into drug candidates, simultaneously, yet in coordination with one another.

“I think a strategic change from individual grant funding to a collaborative, strategic program funding approach is a major paradigm shift,” Dr. Webster Cavenee, a Defeat GBM advisor, said at the time. “And I think this kind of shift will allow us to make progress faster. Everybody recognizes that to defeat GBM, we really have to have a concerted effort like this.”

“One of the reasons that the scientific process is often slow in turning knowledge into outcomes for patients is because the ecosystem of science is a complicated one,” says Dr. Paul Mischel, one of the Collaborative’s leading researchers from Ludwig Cancer Research. “It’s very hard to be able to have the pieces in place to interact rapidly. The Defeat GBM program is almost like a catalyst – it puts together the pieces that allow progress to move much more quickly.”

Scientifically, the strategy is to take a “whole cloth” approach toward discovering and developing precision medicines for GBM patients. The scope of the scientific endeavors covers the entire spectrum of preclinical research, from basic science to translational research and early-phase clinical trials, broken out into four interrelated “Cores” of project teams, each led by a number of experts in the field.

“One of things that’s been quite terrific about the Defeat GBM program is that there is a structure and set of collaborative arrangements in place that allow investigators to go from discovery, potentially, to things we can actually do about it in the clinic,” says Dr. Mischel. “The integration of fundamental discovery, translation, and clinical work is really critical and a key aspect of agency that the National Brain Tumor Society is doing to empower scientists and clinicians to make a difference. It’s been really an extraordinary and interactive program and, I think, way ahead in its thinking about how science needs to be done in order to make a difference for patients.”

Now, halfway through Defeat GBM’s five-year, $10 million commitment, the collaborative has contributed to breakthrough findings on GBM tumor biology and is bringing forth a host of both new therapeutic targets and potential drugs of interest for evaluation in potential future clinic trials, with the ultimate hope of receiving approval as new treatment options for GBM patients.

The research centers on understanding why, to date, virtually every attempt to treat GBM has been unsuccessful.

“This is a devastating cancer and there hadn’t really been any advances in the field,” says Dr. Mischel. “Now, in the past 20 years there’s really been a sea-change where our understanding of the biology of the disease is really quite sophisticated. The challenge in front of us now is to be able to use those advances for the benefit of patients.”

In other words, from years of intense study there is actually a good deal we know about what is going wrong in the cells causing GBM tumors to grow so aggressively. Yet, researchers are yet to understand how to exploit this information to develop effective treatments for GBM patients.

“The knowledge base is incredibly deep in many ways,” says Dr. Mischel. “The map of the genes that make proteins, and their alterations, in this cancer has largely been identified. So one would expect or anticipate that this would actually make a difference in the lives of patients. But for a variety of reasons…that information has yet to really benefit patients.”

Thus, while the scientific research underlying the Collaborative is intense, sophisticated, and truly leading-edge, the theory behind it is actually quite simple: In order to develop new, effective treatment strategies for GBM patients, the Collaborative needs a better understanding of how these tumors are protecting themselves from, or escaping, the effects of current treatments; find vulnerabilities in these tumors (their Achilles heel); create better laboratory models to recreate these effects for use in studies; and then test potential drugs against these mechanisms with the goal of identifying ones that could stop them.

And, collectively, in just two-and-a-half years the Defeat GBM team has been able to generate a tremendous amount of progress in this area:

  • Through discovery research, Defeat GBM researchers have identified 19 potential novel therapeutic targets for possible new GBM treatment strategies to be developed in the future.
  • Through both these new discovery efforts and screening more than 1,000 chemical compounds and existing drugs (and 75,000 combinations thereof) for potential tumor-fighting activity against GBM tumors in newly created laboratory models, the team has identified 16 drugs, categories of drugs, combinations, or treatment approaches of interest to study further to determine if they could ultimately be effective treatments for GBM patients.
    • Of the 16, eight (8) classes of drugs have been prioritized for further evaluation and analysis of their tumor-fighting potential.
    • Four (4) of the eight, have been further categorized as clinical candidates with hopes of rapid translation to early clinical trials for patients.
  • Identified nine (9) possible new biomarkers to help predict and monitor patient response to GBM treatments

Additionally, the team has:

  • Developed, characterized, and validated more than 70 new laboratory models based on tissue taken from GBM patients, which more faithfully mimic the behavior of human glioblastoma tumors, for use in preclinical drug screening.
  • Published 29 papers and reviews in high-impact scientific/medical journals, which have collectively been cited more than 300 times by other journal publications, demonstrating their importance to providing critical new information to the brain tumor research field

“The Defeat GBM program is reaching a tipping point, with researchers nearing the juncture of moving a number of novel therapeutics into the clinical testing phase,” said Dr. W.K. Alfred Yung of MD Anderson Cancer Center and Defeat GBM’s Scientific Director. “Our team is anxious and excited to continue our momentum and develop a multitude of potential new treatment approaches for patients in desperate need of new options.”

View the full Defeat GBM 2017 Progress Report here.

As the stakes gets higher with each new discovery, and the push toward the clinic moves closer, so too does the cost and the resources needed to meet the challenges and opportunities ahead (clinical research is typically the most expensive phase of drug R&D). Thus, the Defeat GBM Research Collaborative is currently seeking to expand via partnerships, sponsors, and dedicated supporters that share in the common mission of forever changing the trajectory of this terrible disease.

If you wish to support the Defeat GBM Research Collaborative, please visit here. 

  • Nelson Ayala

    you mention drugs, combinations of, treatment approaches, etc, but what actually is according to the group (or anyone else out there) the most effective or producing the best results? with the understanding that each patient/tumor reacts differently to each one of these. There are so many trials out there and impossible for us or our doctors to find the best one for each individual case.

    • TomHalkinNBTS

      This is a very important point, and challenging issues. Finding the right drug(s), for the right patient(s), at the right time(s), is the ultimate goal of precision medicine. To do this well, “biomarkers” will likely need to play a major role in clinical research (trials) and clinical care. Biomarkers – specifically predictive molecular markers – have the potential to help researchers and doctors understand which patients are most likely to benefit from which treatment(s), and assign therapy and direct treatment that way. If you have not already, I suggest reading the deeper-dive series on Defeat GBM we began recently, particularly starting with our Biomarkers Core blog. See here: http://blog.braintumor.org/defeat-gbm-research-collaborative-core-by-core-progress-biomarkers-core/

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