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Defeat GBM

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Defeat GBM

Source: http://defeatgbm.org

Glioblastoma multiforme (GBM) is the most common, complex, treatment resistant, and deadliest type of brain cancer, accounting for 45% of all brain cancers, with nearly 11,000 men, women, and children diagnosed each year. The time is now to make progress against this disease!

The Defeat GBM Research Collaborative is a groundbreaking, research-based initiative that takes advantage of the convergence of exciting scientific advancements, an innovative business model, and support from biopharmaceutical companies to drive research forward with the aim of doubling the five-year survival rate of GBM patients. Building from the pioneering data discovered through The Cancer Genome Atlas (TCGA) and the growing commitment to true collaboration across disciplines and institutions, we have entered a new era of possibilities. All members of the Defeat GBM Research Collaborative share real-time information of one another’s cutting-edge research to quicken the pace of translating discoveries into clinical stage research—cutting years out of the traditional clinical trial research and analysis procedure. Together with your support, we can bring change today!

 

 

About the Defeat GBM Research Collaborative
Defeat GBM Impact
The Defeat GBM Research Collaborative formalized in 2013 and initiated its research programs in 2014. In this short time it has already proven that its unique research model can be successful in contributing state-of-the-art scientific discovery and to applying this learning for drug development and clinical evaluation. In the first 18 months, Defeat GBM research has generated a prolific number of publications contributing important new insight into the mechanisms and biomarkers of acquired drug resistance in GBM patients. This knowledge will form the basis of developing future Defeat GBM strategies to overcome as well as monitor the development of resistance to therapies. In addition the Defeat GBM team is strategically involved in an unprecedented global adaptive clinical trial for GBM patients. This accelerated transfer of findings from the Discovery core to the Clinical Trial research core is a testament to the enhanced collaboration and progress made possible by the leading-edge structure of the Collaborative.

Defeat GBM: Project Overview
Glioblastoma is a disease of frequent genetic alterations and targeting the aberrations in such molecular pathways is a current focus of novel treatment development for GBM. However, studies have shown that GBMs can adapt to targeted treatments and acquire drug resistance. To develop more effective treatments and define appropriate drug combinations, the identification and validation of robust targets that drive malignancy needs to be accompanied by the identification of resistance mechanisms. The Defeat GBM initiative is made up of four interrelated research cores that encompass 1) Target Discovery 2) Drug Development 3) Biomarker Development and 4) Innovative Clinical Trials.

Led by top cancer researchers and clinicians, all simultaneously conducted projects span the key areas of drug discovery and development where better knowledge and progress are required to advance the field and improve the lives of patients. Each team will follow the same goals to achieve real progress on defined objectives over a multi-year, deadline-driven agenda to:

Quicken the Pace of Discovery – More basic scientific research is vital to identify the right targets and associated resistance mechanisms of GBM.
Transfer Target Knowledge to Drug Development – Once the targets are identified, focus on testing compounds and drugs against the targets to block the cancer-activating genes, pathways, and associated resistance mechanisms with the right drugs.
Identify Patient Biomarker Panels to Improve Clinical Trial Success – Use new data about targets to create diagnostic tools that will help select the right patients for the right treatments and test the therapies to achieve clinical trial success.
Conduct Innovative Clinical Trials – Take advantage of the study of genetic alterations, systems biology, and molecular profiling of GBM patients to develop trials that are faster, more focused, and less costly so that the right therapies can be delivered to the right patients quickly.
Defeat GBM Oversight
In partnership with the Strategic Scientific Advisory Council, the Initiative is chaired by Scientific Director, Dr. W. K. Alfred Yung, MD Anderson Cancer Center, and Cure GBM LLC, a subsidiary of National Brain Tumor Society, to oversee the Defeat GBM Research Collaborative and ensure attainment of key milestones and overall goals which are a prerequisite for continued project funding.

 

 

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 Webster Cavenee, PhD, and Frank Furnari, MD, 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 W.K. Alfred Yung, 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 and Webster Cavenee, PhD, Ludwig Institute for Cancer Research, University of California, San Diego
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 subā€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

 

 

 

Strategic Scientific Advisory Council (SSAC)
A team of senior brain cancer experts acting as the Strategic Scientific Advisory Council (SSAC) will oversee the Defeat GBM Research Collaborative to ensure goal attainment and overall success. In addition, the Advisors will play a key role in attracting and evaluating additional GBM research projects taking place throughout the United States, as well as around the world. Additional projects will be evaluated on their scientific potential, as well as their ability to support the patient-centric and outcome-driven goals of Defeat GBM. With this lens, the Advisors will help to ensure that only the most promising science is funded and include:

Anna Barker, PhD - Arizona State University
Mitchel S. Berger MD, FACS, FAANS - University of California, San Francisco
Darell D. Bigner, MD, PhD - Duke University
Webster Cavenee, PhD - Ludwig Cancer Research
George D. Demetri, MD - Senior Vice President for Experimental Therapeutics
Richard B. Gaynor, MD - Eli Lilly and Company
William C. Hahn, MD, PhD - Deputy Chief Scientific Officer; Chief, Division of Molecular and Cellular Oncology
W. K. Alfred Yung, MD - The University of Texas MD Anderson Cancer Center
Anna Barker, PhD
Arizona State University
Anna Barker, PhD
Dr. Anna Barker was former Deputy Director for Strategic Scientific Initiatives at the National Cancer Institute. At the NCI, Barker developed a number of strategic programs focused on the development of knowledge networks that emphasized innovation, publicly available data, team science, and convergence of the biological and physical sciences. Some of the programs planned and developed under her leadership included: The Cancer Genome Atlas, co-developed with the National Human Genome Research Institute to identify all genomic and molecular changes in cancer; the Nanotechnology Alliance for Cancer, a network dedicated to developing and applying nanotechnologies; and the Physical Sciences Oncology Centers that connects physicists, mathematicians, engineers and cancer scientists dedicated to developing a fundamental understanding of cancer.

Dr. Barker completed her Ph.D. at the Ohio State University, where she trained in immunology and microbiology. Her research interests include experimental therapeutics, tumor immunology, and free-radical biochemistry in cancer etiology, prevention, and treatment.

Dr. Barker has a long history in the performance and management of biomedical research, technology transfer, development and product commercialization in the nonprofit and private sectors. Her research interests have been primarily in drug discovery, development, and immunotherapy development. Prior to entering the biotechnology sector, she was a senior executive at Battelle Memorial Institute.

In the private sector, she co-founded and served as the chief executive officer of a public biotechnology therapeutics development company, and subsequently founded and led a private company dedicated to the transfer and deployment of technologies to prevent and treat cancer. She has received a number of awards for her volunteer and philanthropic activities, including a fellowship in basic science from the American Association of Cancer Research.

Dr. Barker was a co-recipient of the 2009 National Brain Tumor Society Research Excellence Award for her work on the The Cancer Genome Atlas (TCGA).

Mitchel S. Berger MD, FACS, FAANS
University of California, San Francisco
Mitchel S. Berger MD, FACS, FAANS
Dr. Mitchel S. Berger, Chair of Neurological Surgery at the University of California, San Francisco, is a nationally recognized expert in treating brain and spinal cord tumors, as well as tumor-related epilepsy in adults and children. He is also a specialist in brain mapping techniques, used to identify areas of motor, sensory, and language function during surgery, and an expert in the use of the Gamma Knife for tumor treatment. He is co-Director of the Adult Brain Tumor Surgery Program, Director of the Brain Tumor Research Center, Director of the Center for Neurological Injury and Repair, and Director of the Adult Hydrocephalus and Shunt Program. Dr. Berger also practices in the Neuro-Oncology Program and the Radiosurgery Program.

Dr. Berger earned a bachelor’s degree from Harvard in 1975 and a medical degree from the University of Miami School of Medicine in 1979. He completed an internship and residency at UCSF and was awarded a clinical fellowship in neuro-oncology by the American Cancer Society and a research fellowship with the Brain Tumor Research Center. He completed further fellowship training in neuro-oncology at UCSF and in pediatric neurosurgery at the Hospital for Sick Children of the University of Toronto, Canada. His professional activities include his election to the Board of Directors of the American Association of Neurological Surgeons and his appointment to the American Board of Neurological Surgeons. Dr. Berger is board certified in neurosurgery.

His current research interests involve identifying molecular markers in gliomas as correlates of tumor progression and prognosis. This is done in conjunction with the Molecular Marker Core of the BTRC. Dr. Berger also works with Dr. Krys Bankiewicz to test small molecule inhibitors in brain tumors using the drug delivery technique convection enhanced delivery. In addition, he is a co-Investigator with Dr. John Park in UCSF’s Comprehensive Cancer Center to develop immunoliposome-directed targeted therapy for treating gliomas that express EGF receptors. Other collaborations include functional mapping localization of language pathways in the brain with Dr. Robert Knight and the Cognitive Neuroscience Graduate Program at UC Berkeley. Dr. Berger is currently the Principal Investigator of UCSF’s SPORE Brain Tumor Program, funded by the National Cancer Institute and National Institute of Neurological Disorders and Stroke.

Darell D. Bigner, MD, PhD
Duke University
Darell D. Bigner, MD, PhD
Darell D. Bigner, MD, PhD, started at Duke in 1963 as a medical student and has remained there for the past 41 years, with the exception of two years spent at the NIH (1968-70). He is the Edwin L. Jones, Jr. and Lucille Finch Jones Cancer Research Professor, Director of the Preston Robert Tisch Brain Tumor Center at Duke, and Director of the Pediatric Brain Tumor Foundation Institute at Duke. Dr. Bigner is also co-Program Leader of the Duke Comprehensive Cancer Center’s Neuro-Oncology Program, Vice-Chairman of Investigative Pathology, Director of the Preuss Laboratory for Brain Tumor Research, former Editor-in-Chief of the Journal of Neuro-Oncology, and Chairman of the Scientific Review Board of the National Cancer Center, and the Pediatric Brain Tumor Foundation. Most notably, Dr. Bigner co-founded the Brain Tumor Society’s research grant program in 1991 and served as Scientific Advisory Council Chair for 15 years.

Dr. Bigner is considered one of the leading authorities on brain tumors in the world. He has published more than 400 full-length manuscripts, books, chapters, and reviews, all on brain tumors. His research concerns the cause and improved diagnosis and treatment of malignant brain tumors in adults and children. His laboratory is the lead laboratory in Duke’s Neuro-Oncology Program, and the goals of his lab are to study basic mechanisms of neoplastic transformation and mechanisms of altered growth control in malignant brain tumors and tumors that metastasize to the brain and spinal cord. Monoclonal antibodies developed in Dr. Bigner’s laboratory are currently in clinical trials for patients with malignant brain tumors.

Dr. Bigner was awarded three consecutive MERIT awards by the National Cancer Institute (NCI). The MERIT Award is a highly selective award presented by the National Institutes of Health that recognizes superior researchers who have demonstrated outstanding competence and productivity in research endeavors. MERIT Awards are given only to the top 1% of NCI investigators, and it is extremely rare for anyone to receive three consecutive MERIT awards.

Webster Cavenee, PhD
Ludwig Cancer Research
Webster Cavenee, PhD
Dr. Webster Cavenee is a pioneer in our understanding of the role that hereditary predisposition plays into the development of cancer. In 1991 he became Director of Ludwig Cancer Research, San Diego and Distinguished Professor at the University of California, San Diego.

Dr. Cavenee received his PhD with honors in 1977 from the University of Kansas Medical School and then did postdoctoral work at the Jackson Laboratory, MIT, and the University of Utah. He held faculty positions at the University of Cincinnati and McGill University.

Dr. Cavenee is a member of the National Academy of Sciences, a past-President of the American Association for Cancer Research (AACR), a Fellow of the American Academy of Microbiology, a Fellow for the National Foundation for Cancer Research, and a Fellow of the International Union Against Cancer. He is on the editorial boards of several journals and has served on the Board of Scientific Counselors of the National Cancer Institute and the National Institute of Environmental Health Sciences, as well as numerous advisory boards for philanthropic foundations (including the National Brain Tumor Society and the Brain Tumor Funders Collaborative) and biotechnology companies.

His work on the genetic basis of cancer predisposition and progression comprises more than 300 publications and has been recognized with more than 80 honors and awards, most notably the Rhoads Award of AACR, the Charles S. Mott Prize of the General Motors Cancer Research Foundation, and the Albert Szent Gyorgyi Award. His work in GBM research, including with the Defeat GBM Research Collaborative earned him AACR’s 2014 Margaret Foti Award for Leadership and Extraordinary Achievements in cancer research.

George D. Demetri, MD
Senior Vice President for Experimental Therapeutics
George D. Demetri, MD
Dr. George D. Demetri is a Professor of Medicine at Dana-Farber Cancer Institute/Harvard Medical School and Director of the Center for Sarcoma and Bone Oncology in the Department of Medical Oncology at the Dana-Farber Cancer Institute (DFCI) and Brigham and Women’s Hospital (Boston, Massachusetts). Dr.Demetri is also the Director of Ludwig Cancer Research at Dana-Farber/Harvard Medical School.

Dr. Demetri received his undergraduate degree in Biochemistry from Harvard, and medical degree from Stanford University School of Medicine in 1983. He then went on to an internal medicine residency and chief residency at the University of Washington Hospital in Seattle. He then completed a fellowship in Medical Oncology at the DFCI and Harvard Medical School, where he has served as an Attending Physician since 1989.

Dr. Demetri’s research and clinical interests have focused on the translation of scientific discoveries into targeted drugs for the management of sarcomas as a model for solid tumor research and development. This work has led to the development of the oral drug Gleevec as an effective treatment for the gastrointestinal sarcoma known as GIST, and is continuing with the research leading to the new multi-targeted agent SU11248 for GIST resistant to Gleevec.

A fellow of the American College of Physicians, Dr. Demetri is a member of many professional societies and editorial boards of scientific journals. He is a member of the Board of Directors of the Connective Tissue Oncology Society, the chair of the Medical Advisory Board of the Sarcoma Alliance, and a member of the Medical Advisory Board of the Sarcoma Foundation of America. He has been instrumental in raising awareness of issues relating to sarcoma research and care by his activities on the Internet, and he founded a non-profit educational site for sarcoma patients and their families.

He joins Defeat GBM as a clinical trial design expert that will help translate discoveries from the project into trials.

Richard B. Gaynor, MD
Eli Lilly and Company
Richard B. Gaynor, MD
Richard B. Gaynor, MD, joined Eli Lilly and Company as Vice President for Cancer Research and Clinical Investigation in August 2002. Currently he is Vice President of Clinical Development and Medical Affairs in the Oncology Business Unit.

Dr. Gaynor received a Bachelor of Science degree in biology from Texas Tech University and then received a doctor of medicine degree from the University of Texas Southwestern (UTSW) Medical School. He served his internship and residency in internal medicine at Parkland Memorial Hospital in Dallas, Texas. He completed a fellowship in hematology-oncology at the University of California at Los Angeles (UCLA) School of Medicine and then served on the faculty there. He received board certification in internal medicine, hematology, and medical oncology.

Prior to joining Eli Lilly, Dr. Gaynor was a Professor of Medicine and Microbiology, and held several leadership positions at the UTSW Medical Center in Dallas. He was Chief of the Division of Hematology and Oncology at UTSW, and Director of the Harold C. Simmons Comprehensive Cancer Center there, in addition to his work as the Lisa K. Simmons Distinguished Chair in Comprehensive Oncology. He has also served on numerous National Institutes of Health (NIH) advisory committees and was elected to both the American Society of Clinical Investigation and Association of American Physicians.

Dr. Gaynor is on the editorial board of several scientific journals and has an extensive publication record totaling more than 140 scientific articles. He serves on the board of the Damon Runyon Cancer Research Foundation and the Walther Cancer Institute, as well as on several committees for the American Association for Cancer Research and other leading cancer organizations.

William C. Hahn, MD, PhD
Deputy Chief Scientific Officer; Chief, Division of Molecular and Cellular Oncology
William C. Hahn, MD, PhD
Dr. William C. Hahn is a medical oncologist and Associate Professor in the Department of Medical Oncology at the Dana-Farber Cancer Institute (DFCI), and a Senior Associate Member of the Broad Institute of MIT and Harvard. He directs the Center for Cancer Genome Discovery at DFCI. He is known for his cancer biology expertise and for his leadership role in the Broad Institute RNAi activities, where he serves as co-PI of the RNAi Consortium (TRC), and has led the Center’s efforts in discovering essential kinase in cancer using RNAi.

Dr. Hahn received his MD and PhD from Harvard Medical School in 1994. He then completed clinical training in internal medicine at Massachusetts General Hospital and medical oncology at DFCI. He conducted his postdoctoral studies with Dr. Robert Weinberg at the Whitehead Institute and joined the faculty of DFCI and Harvard Medical School in 2001. He became Board Certified in internal medicine in 1997, followed by medical oncology in 2000. Dr. Hahn completed his Fellowship at Dana-Farber/Partners CancerCare and his Residency at Massachusetts General Hospital.

Dr. Hahn has been the recipient of many honors and awards including a Harvard National Scholarship, a Damon Runyon-Walter Winchell Cancer Research Fund Fellowship, Howard Hughes Medical Institute Pre- and Postdoctoral Fellowships, a Doris Duke Charitable Foundation Clinical Scientist Development Award, the 2000 Wilson S. Stone Award from MD Anderson Cancer Center for outstanding research in cancer, a Kimmel Scholar Award, and the Howard Temin Award from the National Cancer Institute. In 2005, Dr. Hahn was elected to the American Society of Clinical Investigation.

W. K. Alfred Yung, MD
The University of Texas MD Anderson Cancer Center
W. K. Alfred Yung, MD
Professor W.K. Alfred Yung, MD, received his undergraduate degree from the University of Minnesota, Minneapolis, in 1971, graduating summa cum laude. For his medical training, he attended the University of Chicago Pritzker School of Medicine and received his MD degree in 1975. Internship and residency training followed at the University of California, San Diego from 1975-1978, and chief residency and fellowship at Cornell University School of Medicine and Memorial Sloan Kettering Cancer Center from 1978-1981. Dr. Yung currently holds the title of Professor of Neuro-Oncology and Cancer Biology, as well as the Margaret and Ben Love Chair of Clinical Cancer Care at MD Anderson Cancer Center. He has served as Chair of the Department of Neuro-Oncology since 1999 and leads MD Anderson’s Brain Tumor SPORE. He is also Professor of Neurology at the University of Texas Health Sciences Center at Houston Medical School and serves on the faculty of the University of Texas Graduate School of Biomedical Sciences in Houston. Dr. Yung is the former Editor-in-Chief of Neuro-Oncology, co-Chair of NCI’s Brain Malignancies Steering Committee, and has been named as one of the Best Doctors in America every year from 1992 to the present.

His research program at MD Anderson Cancer Center spans more than two decades and includes basic, translational, and clinical research. Along with three years of continuous funding by NCI, his work has also been funded by foundations and industry grants. His primary research interest focuses on development of molecular therapeutic strategies targeting the EGFR and PTEN/PI3 kinase pathways and the angiogenic regulatory mechanisms that are crucial to human glioma genesis and progression. The translational research effort has developed several adenoviral vectors that are capable of down-regulating TGF-α and VEGF production and angiogenesis in glioma cells. More recently, his laboratory has focused on investigating the biological activity of a series of new PTEN/PI3K pathway inhibitors in glioblastoma in vitro and in vivo models. Another research project investigates the subcellular localization of the tumor suppressor MMAC/PTEN gene and its nuclear signaling pathway.

Parallel with Dr. Yung’s laboratory research focus, is his work as principal investigator on the NCI-sponsored Brain Tumor Consortium phase I and II trials of several newly developed agents and novel combinations of targeted inhibitors designed to attack multiple involved pathways of cancer.

 

 

Latest Updates
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