Spotlight on Research
Collaboration – Accelerate Brain Cancer Cure and Duke University

The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center is one of the largest and most successful in the field.  While Duke researchers and clinicians work to develop more effective techniques for surgery, chemotherapy, and radiation therapy, their research efforts are also devoted to improving the quality of life for patients and their loved ones.  Accelerate Brain Cancer Cure shares a passionate commitment with Duke – a focus on making existing treatments more effective, discovering new treatments, and ultimately, finding a cure for brain cancer. 

A History of Collaboration

Accelerate Brain Cancer Cure founder Dan Case identified these shared goals when he started the organization in 2001 and invited Drs. Darell Bigner and Henry Friedman to the early planning and development meetings for our organization.  Dr. Bigner is considered one of the leading authorities on brain tumors in the world.  He is a neuropathologist focused on research concerning the cause and improved diagnosis and treatment of malignant brain tumors in adults and children and currently serves as the director of the center.   Dr. Friedman, a deputy director at the center, is an internationally recognized neuro-oncologist with a career-long interest in the treatment of children and adults with brain and spinal cord tumors. 

The initial connection has grown into a $5 million Accelerate Brain Cancer Cure investment in Duke’s programs, a results-focused collaboration that supports the development of breakthrough therapies for brain tumors.  So what goes into an “effective partnership” – is it trust, flexibility, commitment, shared values, or successful results?  For this partnership, it has been a combination of all of the above. 

Accelerate Brain Cancer Cure and Duke share a focus on the best utilization of all existing resources and, while pushing innovation, remaining strategic and results-focused.  “During the more than 30 years that I have spent in research, working to improve diagnosis and treatment of brain tumors, I have never seen an organization have as much impact in as short a period of time,” said Dr. Bigner.  “Accelerate Brain Cancer Cure energizes the research community and fosters collaboration between academia and industry and its work in expediting clinical trials of new, rationally designed therapies has been instrumental in moving the field forward.”

Discovering New Therapies

Duke’s researchers are on the cutting edge of developing new therapies for patients and some of the most exciting brain tumor research to date has surrounded bevacizumab (Avastin). In a recent pilot study published in the Feb. 20, 2007 issue of the journal Clinical Cancer Research, Duke researchers reported that dual therapy with Avastin and the chemotherapy drug (irinotecan) either shrank tumors or restricted their growth in nearly all cases (32 patients with recurrent cancerous brain tumors) for up to three months longer than comparative therapies. “These results are exciting because of the possible implications for a patient population that currently has the poorest possible prognosis going into treatment, those with malignant brain tumors that have recurred after initial treatment,” said Dr. Friedman.

Duke is now participating in an 11-center trial of this combination therapy funded by Genentech, and it is hoped that the results will lead to an FDA approved therapy for patients with brain cancer. “Going forward, we will also explore the efficacy of this treatment in newly diagnosed patients," Dr. Bigner said. "Ultimately, our hope is that this will offer a real weapon in what is now a very limited arsenal for treating a very challenging cancer.”

Funding New Potential Discoveries

Together, Accelerate Brain Cancer Cure and Duke developed the Preclinical Screening Program, a major project that emerged in the earliest days of Accelerate Brain Cancer Cure.  The goal of the collaboration was to rapidly move potentially life-saving drugs from the laboratory to the clinic in an effort to save brain tumor patients who have little time and limited therapeutic options available to them. 

The Preclinical Screening Program was designed to establish a critical missing link between the biopharmaceutical industry’s efforts to produce potentially life-saving drugs and the still theoretical knowledge at the cutting edge of scientific inquiry.  The program evaluates approved and experimental drugs thought to have potential utility against brain cancer. 

Because the development of new drug therapies is typically expensive, laborious, and time-consuming to undertake, few companies can afford to invest their research dollars in the search for a cure for diseases, like brain cancer, that affect a comparatively small percentage of the population.  Dr. Bigner explains, “Accelerate Brain Cancer Cure’s funding enables researchers from any sector to submit compounds to Duke for screening and encourages researchers in academia, corporations, and federal agencies to test both marketed and experimental therapies that target other types of cancer for their potential benefit to brain cancer patients.” 

Results

To date, more than 150 compounds have been tested or are under consideration for this program. The researchers at Duke have initiated trials for 18 therapies in brain tumor patients on the basis of results obtained through the Duke Preclinical Screening Program.  In addition, testing results helped strengthen the rationale and thereby indirectly facilitated the clinical testing of six additional therapies under investigation at Duke through other funding sources.

An important outcome of this program and measure of its success is the advancement of candidate brain cancer therapies from the laboratory to the clinical trial setting for efficacy and safety testing in patients.  “This partnership has become particularly important as both Duke and Accelerate Brain Cancer Cure are committed to giving patients every possible chance at a future," said Dr. Friedman.

Supporting Leading Researchers

Through the years, Accelerate Brain Cancer Cure has also funded several renowned Duke University researchers, including Drs. John Sampson, Jeremy Rich, Timothy Stenzel, and Matthias Gromeier with Accelerate Brain Cancer Cure Project Awards.  These awards support leading investigators with novel translational research ideas that hold significant near-term potential to hasten a cure for brain cancer.

IMMUNOTHERAPY
John Sampson, M.D.
Duke University


Accelerate Brain Cancer Cure is funding Dr. Sampson’s work to develop a cancer vaccine for glioblastoma with a 2006 Project Award.  Dr. Sampson is looking to establish a new therapy for brain cancer that will restrict damage to non-cancerous brain tissue.  Dr. Sampson is evaluating how the immune system, which is designed to differentiate normal from abnormal or even cancerous tissues, can be involved in fighting cancer.  He believes that a number of methods can be used to train the immune system and, specifically the T-cells of patients, to fight cancer.  These methods include vaccines and strategies called, “adoptive T-cell therapy.”

Dr. Sampson and his colleagues have recently made some important discoveries to enhance approaches toward fighting tumors. The first is the discovery that proteins from the common cytomegalovirus (CMV) are produced in malignant brain tumor cells, but not in normal surrounding brain tissue.  Because these viral proteins are foreign to people, they can induce very strong immune responses.

Patients with malignant gliomas often have suppressed immune systems – the cause for which has remained a mystery for over 30 years.  Recently, Dr. Sampson and his team demonstrated that patients with brain cancer have increased percentages of regulatory T-cells, which may be responsible for their suppressed immune systems.  By removing these regulatory T-cells, the immunosuppressive effects are reversed, and normal immune responses are obtained.  The overall goal of this project is to demonstrate that the removal of the regulatory T-cells prior to therapy in GBM patients will generate enhanced anti-tumor immune responses without initiating autoimmunity and thereby help optimize this promising therapeutic approach.

CANCER STEMS CELLS
Jeremy Rich, M.D.
Duke University 


Supported by Accelerate Brain Cancer Cure, past Project Award winner and Duke University researcher, Dr. Jeremy Rich has been working on novel research to accelerate brain cancer therapies through a variety of projects.

Dr. Rich’s recent contributions have been in the field of cancer stem cell research.  He and his research team established that cancer stem cells activate a specific protective response that enables them to repair damage caused to their DNA and thereby survive exposure to radiation.  These findings help to explain why certain malignant tumors are resistant to radiation therapy.  Dr. Rich’s team also found that treating cancer stem cells with drugs that disrupt this protective process causes them to become more sensitive to the cell-killing effects of radiation.

Although cancer stem cells make up less than four percent of a cancerous tumor, they are believed to be responsible for orchestrating tumor growth. While other cancerous cells in the tumor mass can cause damage by their sheer bulk, cancer stem cells alone drive tumor formation. Dr. Rich explains, “Because of the cancer stem cell's unique replenishment properties, we hypothesize that novel cancer therapies can be discovered to specifically target and eradicate these cells.”

Dr. Rich leads a dedicated team from Duke University that is aggressively pursuing research to identify and target cancer stem cells in glioblastoma. “We can both advance promising new treatment strategies for glioblastoma by targeting a novel marker on cancer stem cells and investigate the use of the marker for early detection of malignant, recurring tumor,” he said.

Dr. Rich’s latest findings in this area were featured in the October 10, 2021 journal, Nature.

Looking Ahead

Each of these programs with Duke represents a mutual commitment to finding a cure for brain cancer and moving the field forward through innovative cooperation.  We believe the best way to move forward, faster, is to work together.  Accelerate Brain Cancer Cure is proud of its continued partnership with Duke University and will keep laser-focused on future collaborations with a focus on bringing new, effective therapies to the patients and families who need them. 

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