The Preston Robert Tisch Brain Tumor Center conducts groundbreaking research and offers innovative treatment for brain tumors. It is dedicated to caring for pediatric and adult patients and their families, improving their quality of life, and ultimately finding a cure for brain tumors.
Visit DukeHealth.org for more information about glioblastoma and other primary brain tumors.
The Preston Robert Tisch Brain Tumor Center is one of the first brain tumor research and clinical programs in the United States. The center has more than 250 full-time employees devoted exclusively to neuro-oncology. It encompasses basic, translational and clinical research, adult and pediatric clinical care services, and quality of life/supportive care programs.
Approximately 900 new adult brain tumor patients and 80 new pediatric brain tumor patients come to the Center each year from around the world. We care for all types of brain tumors, including glioblastomas, meningiomas, and benign brain tumors. We develop a personalized approach for each patient.
The pediatric neuro-oncology program has specific expertise in immunotherapy. We are part of the Pacific Pediatric Neurology Consortium (PNOC) and the COllaborative NEtwork for Neuro-oncology Clinical Trials (CONNECT). Together, we seek to develop new therapies and improve outcomes for children and young adults with brain tumors.
The Preston Robert Tisch Brain Tumor Center's research program is dedicated to finding better outcomes for brain tumors. Novel immunotherapies, including cancer immunotherapy with viruses, immunotoxins, vaccines, and others, were co-developed at Duke to generate tumor immune surveillance fighting cancer in the brain. Through our clinical trials, you may be eligible for studies that use novel therapies to treat brain tumors.
We continue to explore ways to selectively target tumors, tame fast-growing and drug-resistant tumors, and design new therapies to destroy cancer. Our researchers are also studying ways to manipulate the genes and proteins that fuel tumor growth.
Our researchers receive approximately $14.4 million in grant and contract support. Three of the Center’s faculty members (Darrell Bigner, Henry Friedman, and Roger McLendon) are among the top 20 most cited authors on “glioblastoma” in the world.
Training future neuro-oncology providers and scientists are part of the Center’s mission. The robust training program focuses on students at the high school, undergraduate, pre-doctoral, and post-doctoral levels. Most investigators train one or more students in their laboratories each year. We also offer fellowships in adult neuro-oncology and pediatric neuro-oncology.
Zach Reitman, MD, Ph.D., was recently awarded a Mentored Clinical Scientist Research Career Development Award from the National Cancer Institute titled "Enhancing the Efficacy of Radiation Therapy for brainstem glioma by Targeting ATM."
The award, which went into effect on August 1, provides salary support for career development and totals $1.1M over five years.
"The goal of the K08 award is to help me build up my brain tumor research program," said Reitman. "A key component of the award is mentorship from Dr. David Kirsch, a world expert on genetically engineered mouse models and radiation biology in our department, and Dr. David Ashley, the director of the Preston Robert Tisch Brain Tumor Center.The K08 will help me determine if the immune system helps mediate treatment responses in childhood brain tumors.The results will help design the next generation of clinical trials.I will use cutting-edge genetically engineered mouse models and single-cell RNA-sequencing approaches to complete the work."
The Reitman Lab was also recently awarded a Chadtough Defeat DIPG (Diffuse Intrinsic Pontine Glioma) New Investigator Award for $250,000 over two years entitled "Dissecting mechanisms of radioresistance associated with p53 mutations in DIPG." Funding for that grant started on July 1.
"The New Investigator Award is helping me to find out why some pediatric brain tumors are resistant to radiation therapy and other treatments," said Reitman. "Completing the work will help design new treatments that overcome resistance and improve outcomes for patients with DIPG, a rare but lethal childhood brain tumor."
This articleoriginally appearedon the Duke Department of Radiation Oncology website and was posted here with the author's permission.
When Joseph O. Moore, MD, came to Duke as a fellow in 1975, he and his mentors treated chronic myeloid leukemia (CML) with a chemotherapy regimen that was like a “wet blanket.” It suppressed the cancer for a few years. “But it didn’t change the trajectory of the disease,” Moore said. Patients developed acute leukemia, which was almost always fatal.
By the early 1990s, younger patients could achieve a cure with a bone marrow transplant, though complications were common. By 1999, Moore was the Duke investigator for a national study of a targeted drug, imatinib, which stops leukemia cells from growing by shutting down a key protein.
When imatinib was approved by the Food and Drug Administration (FDA) in 2001, it transformed CML into a disease easily treated by taking a pill.
When Moore retired from clinical practice in 2019, he was involved in a study following people with CML who had been taking imatinib long term, which showed they could safely stop therapy.
The CML example provides a snapshot of just how far cancer treatment has come in the last 50 years. For many patients, “There’s an expectation of success and people living normal lives,” said Moore, professor emeritus of medicine.
Much of that progress can be traced to research funded by the “war on cancer,” which launched in 1971 when congress passed the National Cancer Act. The act gave the National Cancer Institute (NCI) the authority and funds to create a national cancer program. The backbone is a network of comprehensive cancer centers that provide patient care and conduct rigorous research to find new and better ways to prevent, diagnose, and treat cancer.
Duke Cancer Institute brain tumor researcher Hai Yan, MD, PhD, was awarded theInternational Prize for Translational Neuroscience of the Gertrud Reemtsma Foundationat a ceremony in Cologne, Germany, on August 26, 2021.The prize recognizes Yan’s identification of genetic mutations linked to gliomas, the most common form of primary brain tumors.
Through genomic studies, Yan’s research team found that mutations in the metabolic enzymes IDH1 and IDH2 were present in 70 percent of progressive malignant gliomas. The discovery and subsequent research could provide evidence to support a novel therapeutic approach to the treatment of gliomas.
Yan is the Henry S. Friedman Distinguished Professor of Neuro-Oncology, Professor of Pathology, and member of The Preston Robert Tisch Brain Tumor Center at Duke Cancer Institute.
The International Prize for Translational Neuroscienceawards outstanding basic neurological research and includes a prize of 60,000 Euros. The award has been given to scientists from 12 different countries, whose discoveries and contributions represent original and significant achievements. Darell Bigner, MD, PhD, directoremeritusof the Preston Robert Tisch Brain Tumor Center, received the award in 2008.
This article originally appeared on theDuke Neurosurgery websiteand was mirrored here with permission of the author
Glioblastoma brain tumors are especially perplexing. Inevitably lethal, the tumors occasionally respond to new immunotherapies after they’ve grown back, enabling up to 20% of patients to live well beyond predicted survival times.
What causes this effect has long been the pursuit of researchers hoping to harness immunotherapies to extend more lives.
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“You never know what's around the corner. It could be everything. Or it could be nothing. You keep putting one foot in front of the other, and then one day you look back and you've climbed a mountain.”― Tom Hiddleston
On July 15, 2009, Duke Law School alum and father-of-three Jeff Bradford, then 31, was on his way home from taking an expert witness depositionin Greensboro, North Carolina, when his car was hit by a drunk driver.
In lieu of suing the driver in the aftermath of the accident — his first impulse —the attorney would instead be inspired to form a band and write a song crediting the driver with unknowingly saving his life.
That same summer Tom O’Donnell, then 45, was busy managing a Kerr Drugs in Pittsboro, NC, and looking forward to kicking back on a cruise with his wife and daughter. Tom, who hadn’t run in two decades, would never have believed that completing the Boston Marathon several times over would figure in his vacation plans in the coming years.
In the summer of 2009, Nestor Paonessa, 29, was planning, with his fiancée, a winter beach wedding in Puerto Rico, the birthplace of Nestor’s parents.
If the assistant general manager and personal trainer at Empower Personalized Fitness in Durham had a crystal ball he would have seen that after five years of marriage he and his wife would be hiking the Inca Trail to Machu Picchu (on their bucket list) and building their dream home. What he’d never have imagined was the next uphill climb he'd make.
While all three men were local, Jeff, Tom and Nestor may never have met had it not been for one thing in particular they had in common — something that would radically change the trajectory of each of their lives and land them on the same path, one foot in front of the other. They each had a brain tumor.
After many months of preparation and an extensive review process, Duke Cancer Institute was renewed as a National Cancer Institute-designated Comprehensive Cancer Center for another five-year period.
The award means that DCI retains the elite NCI designation of “Comprehensive Cancer Center”— an honor currently held by only 51 institutions in the country. The accompanying five-year grant, known as the Cancer Center Support Grant (CCSG), supports DCI’s broad range of clinical, research, and educational programs, which aim to reduce the impact of cancer on the lives of people in North Carolina and beyond.
National Cancer Institute-designated cancer centers are recognized for scientific leadership and resources and must meet “rigorous standards” for research focused on new and better ways to prevent, diagnose and treat cancer.
The Duke Comprehensive Cancer Center, now Duke Cancer Institute, was established in 1972 and has benefited from continuous recognition and funding from the NCI since 1973, when it was named as one of the original eight comprehensive cancer centers.
The CCSG is one of the top five oldest continuous NIH grants at Duke. Michael Kastan, MD, PhD, is the executive director of DCI and has been the core grant’s principal investigator since he joined DCI in 2011.
“Under Dr. Kastan’s leadership and expertise, scientific accomplishments with impactful transdisciplinary and translational research that appropriately-address the cancer burden in the catchment area have been achieved,” wrote the NCI review team. “The Institution is nationally and internationally recognized for its high standard of education, and community outreach and engagement are progressing at an outstanding level… The discoveries of new molecular, genetic, genomic, and epigenetic targets and of biological processes in cancer, together with the support of strong shared resources, to the research programs and the accomplishments in clinical trials, add value to the DCI.”
The review documented eight scientific clinical advances — in understanding microenvironment modulation; differentiation therapy in graft versus host disease; vaccine development for brain tumors; drivers in glioma subgroups; discovery of a genetic variation in leukemia that confers risk for other cancers; caspase-3 and radiation carcinogenesis; a new approach to breast cancer radiotherapy; PIK3CA mutations in breast cancer; and the identification of 12 new variants for epithelial ovarian cancer.
And, the committee lauded DCI’s population-based research, including “important advances in cancer risk factors and biomarker discovery,” the refining of screening guidelines, interventions to enhance patient and family experiences, new tech to improve symptom management and patient outcomes, and clinical trials and research to improve transitions-of-care and end-of-life support.
Shaping Cancer Research and Care
Duke Cancer Institute’s catchment area covers more than eight million people in North Carolina (67 counties), southern Virginia (40 counties), and northern South Carolina (6 counties).
More than 70,000 unique cancer patients were seen in fiscal year 2019.
“During this past funding period, DCI structures and programs have matured and prospered, with demonstrable increases in the number of collaborative publications and investigator-initiated clinical trials, numerous examples of high impact science, and significant expansion of community engagement activities,” said executive director of Duke Cancer Institute and CCSG principal investigator Michael Kastan, MD, PhD. “This grant renewal means that DCI continues to be a leader in shaping cancer research and care.”
Duke Cancer Institute is consistently ranked among the top programs for cancer care in America. Its 315 members and 131 associate members include nationally and internationally known scientific and clinical leaders with a broad range of expertise.
Over the past decade, DCI has had two Nobel Laureates. There are nine members of the National Academy of Science, 10 members of the National Academy of Medicine, two members that have been recognized by Time Magazine as the most 100 influential people in the world, and seven members who hold NIH outstanding investigator awards. In addition, multiple DCI members are governor-appointed advisors to the state of North Carolina’s Advisory Committee on Cancer Coordination and Control.
Since 2014, five new strategic-priority centers or initiatives have been established: the Duke Center for Brain and Spine Metastasis at DCI, the Consortium for Canine Comparative Oncology (C30), the Personalized Cancer Medicine Initiative (which includes the Molecular Tumor Board), the DCI Center for Prostate and Urologic Cancers and the Center for Cancer Immunotherapy. These, in addition to the 82-year-old Preston Robert Tisch Brain Tumor Center, will continue to be central drivers of DCI’s activities in the coming years.
Sixty-seven training grants and fellowship awards worth $6.2 million were awarded during the past five years. Duke Cancer Institute remains committed, moving forward, to investing in career training and development for current and future cancer physicians, scientists and health professionals across all its programs.
A genetically modified poliovirus therapy developed at Duke Cancer Institute shows significantly improved long-term survival for patients with recurrent glioblastoma, with a three-year survival rate of 21 percent in a phase 1 clinical trial.
Comparatively, just four percent of patients at Duke with the same type of recurring brain tumors were alive at three years when undergoing the previously available standard treatment.
Phase 1 clinical trial results of the poliovirus therapy are being presented June 26 at the 22nd International Conference on Brain Tumor Research and Therapy in Norway and simultaneously published in The New England Journal of Medicine.
“Glioblastoma remains a lethal and devastating disease, despite advances in surgical and radiation therapies, as well as new chemotherapy and targeted agents,” saidDarell D. Bigner,MD, PhD, emeritus director ofThe Preston Robert Tisch Brain Tumor Centerat Duke and senior author of the study.
“There is a tremendous need for fundamentally different approaches,” Bigner said. “With the survival rates in this early phase of the poliovirus therapy, we are encouraged and eager to continue with the additional studies that are already underway or planned.”
Bigner and colleagues -- including co-senior authorDavid Ashley, PhD, MBBS, and co-lead authorsAnnick Desjardins, MD, andMatthias Gromeier, MD. all in the Department of Neurosurgery – reported median follow-up of 27.6 months in the phase 1 trial, which was launched in 2012 with a young patient who was just entering nursing school. She has since married and works as a registered nurse.
The therapy includes a genetically modified form of the poliovirus vaccine, which is infused directly into the brain tumor via a surgically implanted catheter. Developed by Gromeier in his lab at Duke, the modified virus preferentially zeroes in on tumor cells, igniting a targeted immune response. Gromeier and co-authors recently published astudy in Science Translational Medicinedescribing the mechanism of action for the poliovirus therapy.
An 18-year collaboration with the National Cancer Institute’s (NCI) Experimental Therapeutics (NExT) Program, NCI, part of the National Institutes of Health, and the U.S. Food and Drug Administration enabled the pre-clinical and translational phases of development of this novel therapy for glioblastoma.
“The Duke and NCI teams collaborated extensively on the preclinical work, which has culminated in these clinical trial results,” said Jim Doroshow, MD, deputy director for Clinical and Translational Research at NCI. “This promising approach in glioblastoma therapy exemplifies the strategic investment made by the NCI to support the development of new therapies such as this one from research discovery into clinical trials.”
Initially in the phase 1 clinical trial, the Duke team planned to increase the dosage of the therapy infusion; a safe dose amount is a primary goal of phase 1 studies. But at higher dosages, some patients experienced too much inflammation, resulting in seizures, cognitive disturbances and other adverse events, so the amount infused was reduced. All but 15 of the 61 patients enrolled in the study had one of the lower dosages.
Study participants were selected according to strict guidelines based on the size of their recurring tumor, its location in the brain and other factors designed for patient protection. A comparison group of patients was drawn from historical cases at Duke involving patients who would have matched the poliovirus enrollment criteria.
For all 61 poliovirus patients, the median overall survival was 12.5 months, compared to 11.3 months for the historical control group. Starting at two years after treatment, the survival curves in the two groups diverged.
