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American Association for Cancer Research Recognizes Contributions of Multi-institutional Research Team Against Brain Cancer
(AACR Press Release)
The American Association for Cancer Research (AACR) awarded the Eighth Annual AACR Team Science Award to the Duke University/Johns Hopkins University/National Cancer Institute (NCI) Malignant Brain Tumor Team at the AACR Annual Meeting 2014, held in San Diego, Calif., April 5-9.
The AACR Team Science Award recognizes an outstanding interdisciplinary research team for its innovative and meritorious scientific work that has advanced or will likely advance cancer research, detection, diagnosis, prevention or treatment.
This multi-institutional team, led by Darell Doty Bigner, M.D., Ph.D., director of the Preston Robert Tisch Brain Tumor Center and the Pediatric Brain Tumor Foundation Institute at Duke University School of Medicine, includes 26 faculty members from Duke, Johns Hopkins, and the NCI. The team was selected because of the immense impact their research has had on our understanding of the biology of glioblastoma multiforme (GBM), the most common and lethal type of brain cancer. Fewer than 4 percent of patients survive to five
years following diagnosis.
Working together against this cancer, the team identified several major genetic aberrations in GBM tumors that provided novel insights. One of their first discoveries was the amplification of a gene called GLI in GBMs. This gene has since been found to be a critical component of the Hedgehog signaling pathway and continues to be subject of intense research in both cancer and developmental biology.
Their next major discovery was a deletion mutant of EGFR called EGFRvIII that is exclusively found in GBMs. The team developed, and continues to develop, novel therapeutics targeting these drivers. One of these is an EGFRvIII therapeutic vaccine currently being tested in an international phase III clinical trial. Additionally, they have developed immunotoxins that target both of these drivers. The first clinical trial involving one of these immunotoxins showed that it was safe and that some patients benefited.
They were the first to describe the genomic landscapes of GBMs, reporting the sequence, copy number, and expression of every gene in the human genome in more than 20 cancers. In addition to providing the basic outline of GBM genomics, this work revealed that a gene called IDH1 was mutated in a subgroup of GBMs. They went on to discover that mutations in IDH1, or the related gene IDH2, were mutated in a large fraction of gliomas of various types. IDH1 was the first novel cancer gene to be discovered through unbiased genome-wide sequencing and has had a plethora of diagnostic and therapeutic implications.
One of their latest discoveries was that of mutations in genes (ATRX or TERT) controlling telomere maintenance in both GBMs and lower grade gliomas. In addition to illuminating the biology of these tumors and their potential relationship to normal stem cells, these mutations provide a remarkably simple approach to the diagnostic classification of gliomas based on genetic rather than histopathologic features.
The team also used their molecular analyses of GBM tumors as a foundation to unravel some of the biologic abnormalities that characterize these cancers. This information led them to develop a genetically modified poliovirus that has lost the ability to kill nerve cells and cause poliomyelitis, but retains the ability to kill tumor cells. Early results of a phase I trial testing this oncolytic poliovirus are promising. The AACR Team Science Award, generously supported by grants from Eli Lilly and Company, is presented with the intent to stimulate change within the traditional cancer research culture by recognizing those individuals and institutions that value and foster interdisciplinary team science. The winning team collectively receives a $50,000 prize and is recognized for its scientific accomplishments and leadership role in fostering team science to advance cancer research.
“On behalf of the Duke/Hopkins/NCI Malignant Brain Tumor Research Team, I wish to thank the AACR, Eli Lilly, and the Selection Committee for honoring us with one of the most prestigious awards in cancer research. I am especially gratified as this award recognizes a 30-plus year collaboration between these three research teams which has meant so much to the field and to me personally. I am so excited about the progress we are making on the development of new diagnosis and treatment modalities for malignant brain tumors; we are on the cusp of making a big difference in the lives of many patients. This could not have been possible without the joint efforts between academia, industry, government, and the private sector,” Bigner said.
Honorees are (in alphabetical order):
- Daniel Barboriak, M.D., professor, Department of Radiology, Division of Neuroradiology, Duke University Medical Center, Durham, N.C.;
- Oren Josh Becher, M.D., assistant professor, Departments of Pediatrics and Pathology, Duke University Medical Center;
- Darell Doty Bigner, M.D., Ph.D., director, Preston Robert Tisch Brain Tumor Center and the Pediatric Brain Tumor Foundation Institute, Duke University Medical Center;
- Thomas John Cummings, M.D., professor, Department of Pathology, Division of Pathology Clinical Services, Duke University Medical Center;
- Annick Desjardins, M.D., FRCPC, associate professor, Department of Neurology, Duke University Medical Center;
- Luis A. Diaz, M.D., associate professor of oncology, Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins University School of Medicine; director of translational medicine, Ludwig Center for Cancer Genetics and Therapeutics, SKCCC, Baltimore, Md.;
- Allan Howard Friedman, M.D., neurosurgeon-in-chief, Duke University Hospital; Guy L. Odom professor of neurological surgery; chief, Division of Neurosurgery/Department of Surgery; Duke
University Medical Center; deputy director, Preston Robert Tisch Brain Tumor Center at Duke;
- Henry Seth Friedman, M.D., James B. Powell, Jr. professor of neuro-oncology; professor of pediatrics; associate professor of surgery and medicine; assistant professor of pathology, Duke University Medical Center; deputy director, Preston Robert Tisch Brain Tumor Center at Duke;
- Matthias Gromeier, M.D., associate professor, Department of Surgery, Division of Neurosurgery; Department of Molecular Genetics and Microbiology; Department of Medicine, Infectious Disease, Duke University Medical Center;
- Sridharan Gururangan, M.B.B.S., M.R.C.P., professor, Department of Pediatrics; associate professor of surgery, Duke University Medical Center;
- Yiping He, Ph.D., assistant professor, Department of Pathology, Duke University Medical Center;
- Kenneth W. Kinzler, Ph.D., professor of oncology, SKCCC at Johns Hopkins University School of Medicine; director, Ludwig Center for Cancer Genetics and Therapeutics at SKCCC;
- Chien-Tsun Kuan, Ph.D., associate professor, Department of Pathology, Duke University Medical Center;
- Roger Edwin McLendon, M.D., professor, Department of Pathology; director, surgical pathology; chief, section of neuropathology, Duke University Medical Center;
- Nickolas Papadopoulos, Ph.D., professor of oncology, SKCCC at Johns Hopkins University School of Medicine; director, translational genetics, Ludwig Center for Cancer Genetics and Therapeutics at SKCCC;
- Ira Harry Pastan, M.D., co-chief, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md.;
- Katherine Barnett Peters, M.D., Ph.D., assistant professor, Departments of Medicine and Surgery; director, neuro-oncology fellowship program, Duke University Medical Center;
- Tulika Ranjan, M.D., assistant professor, Departments of Medicine and Surgery, Duke University
Medical Center; B.K. Ahmed Rasheed, Ph.D., assistant professor, Department of Pathology, Duke University Medical Center;
- John Howard Sampson, M.D., Ph.D., M.H.Sc., M.B.A., Robert H. and Gloria Wilkins professor of neurosurgery; professor, Departments of Pathology, Immunology, and Radiation Oncology, Duke University Medical Center;
- Victor E. Velculescu, M.D., Ph.D., professor of oncology; co-director of cancer biology program, SKCCC at Johns Hopkins University School of Medicine; director, cancer genetics, Ludwig Center for Cancer Genetics and Therapeutics, SKCCC;
- Gordana Vlahovic, M.D., M.H.S., associate professor, Department of Medicine; assistant professor, Department of Surgery, Duke University Medical Center;
- Bert Vogelstein, M.D., Clayton professor of oncology and pathology; joint appointment in molecular biology and genetics, SKCCC at Johns Hopkins University School of Medicine; and investigator, Howard Hughes Medical Institute;
- Jason A. Watts, M.D., instructor of medicine, Department of Medicine, Duke University Medical Center;
- Hai Yan, M.D., Ph.D., professor, Department of Pathology, Duke University Medical Center; and
- Michael Rod Zalutsky, Ph.D., Jonathan Spicehandler M.D. professor of neuro-oncology research; professor, Departments of Radiology, Biomedical Engineering, and Radiation Oncology, Duke University Medical Center