Funded by Genentech and matched funds from the V Foundation
The Duke Cancer Institute and the College of Veterinary Medicine at N.C. State University formed a Comparative Oncology Consortium (COC), taking advantage of their expertise and national leadership in their respective disciplines and their geographic proximity. The goals are to collaborate in pre-clinical and clinical cancer research activities in order to advance our understanding of both cancer causation (a high incidence of specific cancers in specific dog breeds provides opportunities to identify new cancer susceptibility genes and environmental factors in cancer causation) and of behaviors and genetics of specific tumor types, as well as to coordinate clinical trials in humans and canines so that novel therapies can be tested in both settings, with information gained in one setting informing the other. In addition to response outcomes of these cancer therapies, the ability to use biomarkers and pharmacology in the canine models can be a novel addition to the characterization of these new cancer therapies and these insights could result in significant enhancements of clinical trial designs (including dosing, scheduling, and combination therapies) when these treatments are tested in human clinical trials. Cost savings and improved clinical trials design would help encourage pharmaceutical companies to use the canine models as part of the assessment process and would benefit the canine patients by giving them access to these novel therapies.
V Scholar Plus Award- extended funding for exceptional V Scholars
Cancers are diseases caused by faulty genes. Finding these faulty genes will provide effective targets for treatment. To this end, researchers have discovered many gene mutations in all kinds of cancers. However, cancer cells can acquire random mutations, as they are highly unstable. Thus, it is critical to find out which mutations play a causal role in cancer.
To address this problem, we have developed a novel method for studying cancer mutations. We used stem cells to create breast cancer models carrying patient relevant mutations. Using these models, we will study which mutations are responsible for the resistance to cancer treatment. We focus on the treatment that block an important cancer gene, PI3 Kinase. Faulty activation of this gene has been found in many breast cancers. Thus, it is an important cancer target. We have found a specific gene mutation that causes the resistance to this treatment. In this project, we will understand how does this mutation cause the resistance. Based on our mechanistic finding, we will also develop new strategies to overcome the resistance. Thus, successful outcomes of our study will aid the development of effective cancer therapies.
The promise of cancer therapies that target the mutationally activated “drivers” of malignant behavior is that highly selective drugs can be developed that will be effective with minimal side effects. However, that promise has not been achieved because most cancers rapidly develop resistance to these targeted therapies. Recent experience with the leukemias and lymphomas that respond to the drug ibrutinib provide a sobering example of both the successes and disappointments of these targeted approaches. Whereas many patients with malignancies of B-cells (Chronic Lymphocytic Leukemia (CLL), Mantle Cell Lymphoma (MCL) or Diffuse Large B-Cell Lymphoma (DLBCL)) show a beneficial response to treatment with ibrutinib, the responses are generally incomplete and often are not durable. The goal of the collaborative research proposal from UVA and VCU is to elucidate the important mechanisms of intrinsic and adaptive resistance to therapies for B-cell malignancies, and use this understanding to develop RATIONAL combinations of drugs that target both the driver of malignancy and the resistance mechanisms. The two groups have over the past few years taken complementary approaches to tackling this problem, and some of these discoveries are now entering clinical trial. The UVA and VCU groups will utilize materials from these clinical trials, as well as preclinical models and patient samples to develop tools to match patients with the most appropriate drug combinations, and to develop additional combinations of targeted therapies that will have deeper and more long-lasting benefits.
In an effort to better understand and meet the needs of women in the Hispanic community, Fox Chase Cancer Center is launching an initiative to learn more about their preferences regarding messages that inform and announce the availability of clinical trials for women with breast cancer.
Fox Chase will host a series of focus groups in order to seek guidance from the community on the impact of current announcements, gauge awareness of the availability of clinical trials options and understand how the messaging can be better enhanced in order to make the value of participation in research studies higher-impact.
We will host two focus groups of 10 women each. Focus group 1 will review the existing, Spanish-written brochure and will complete both pre- and post-user testing. Focus group 2 will review the verbal PSA version of the Spanish-written brochure and will also complete pre- and post-user testing. Using the information and feedback gathered from these focus groups, we will tailor our message moving forward to better increase knowledge about the existence, importance and education regarding the availability of clinical trials to minority women in North Philadelphia.
With a better understanding in place, we hope to see an increase in the number of diverse women joining breast cancer clinical research studies to better reflect the racial and ethnic mix of the clinical patient population.
The Robert Shields Memorial Grant for Esophageal Cancer was funded by two fundraisers organized by Frank Cannata: Rolling Thunder’s 2015 “Ride for Freedom,” and The Cannata Report Awards and Charities Dinner
Unlike treatment of other common diseases, cancer therapy is constantly limited by rapid evolution of resistance in the treated (cancer) cells. Unfortunately, the amazing capacity of tumor cells to evolve resistance strategies limits virtually every treatment so that metastatic cancers generally remain fatal.
We propose that, while the ability to evolve confers a great advantage on cancer cells, it also imposes a subtle opportunity for treatment. This is because evolving populations can only adapt to current conditions – they can never anticipate future environments. Importantly we can. In this project we employ a sequence of treatments. The first therapy both actively kills cancer cells and guides the evolution of cancer cells so that development of resistance, although inevitable, uses a cellular strategy that we can attack with the second line therapy. We term this “double bind” cancer treatment strategy. An excellent illustration of this approach is pest management through “predator facilitation.” For example, in the event of a rodent infestation, a farmer may introduce an owl. However, rodents typically adapt to the owl predation by shifting their activity to the safety of shrubs. While this would seem to be discouraging result (similar to evolution of resistance to therapy in cancer), the “resistance” strategy can, in fact, be exploited by the farmer by introducing snakes. This is a double bind because the owls facilitate the hunting success of snakes and vice-versa. In this project we construct a similar evolutionary dynamics for treating esophageal cancer using a combination of target therapy and immunotherapy.
Funded by the Dick Vitale Gala in memory of Chad Carr
Approximatively 10 percent of deadly brain tumors in children are diffuse intrinsic pontine gliomas (DIPG), an aggressive cancer that impacts the body’s most vital functions such as breathing and heart rate. DIPG originates from a genetic mutation and creates an environment that hides cancer cells from the immune system, preventing it from recognizing and fighting the disease. While the prognosis for DIPG has not significantly improved in 25 years, immunotherapy — an approach that encourages the immune system to protect against malignant tumors — has yielded remarkable results in patients with otherwise incurable cancers. Support from the V-Foundation will help U-M scientists as we seek to identify which genetic mutations in DIPG can be targeted in each patient to restore the immune function, either alone or in combination with other immunotherapeutic methods.
Dr. James M. Ford, M.D., is an Associate Professor of Medicine, Pediatrics and Genetics at Stanford University School of Medicine. He is the Director of the Stanford Cancer Genetics Clinic and the Stanford Clinical Cancer Genomics Program. A recipient of The V Foundation Translational Research grant in 2002, Ford joined the Scientific Advisory Committee in 2003.
Dr. Ford’s research goals are to understand the role of genetic changes in cancer genes in the risk and development of common cancers. He studies the role of the p53 and BRCA1 tumor suppressor genes in DNA repair, and uses techniques for high-throughput genomic analyses of cancer to identify molecular signatures for targeted therapies. Dr. Ford’s clinical interests include the diagnosis and treatment of patients with a hereditary pre-disposition to cancer. He runs the Stanford Cancer Genetics Clinic, that sees patients for genetic counseling and testing of hereditary cancer syndromes, and enters patients on clinical research protocols for prevention and early diagnosis of cancer in high-risk individuals.
Ford graduated Magna Cum Laude with a B.A. degree from Yale University in 1984 and earned his M.D. degree from Yale in 1989. He has been at Stanford ever since, serving as an intern, resident and fellow before earning his postdoc and becoming Assistant Professor in 1998.
V Scholar Plus Award- extended funding for exceptional V Scholars
Myeloproliferative neoplasm (MPN) is a chronic blood cancer without curative treatments. In MPN, blood stem cells obtain mutations that result in excessive numbers of blood cells. Mutations in a gene named calreticulin have been recently found in a large percentage of MPN patients. It is unknown how calreticulin mutations drive MPN. Our goal is to identify how calreticulin mutations cause MPN and to develop drugs targeting calreticulin to treat this disease.
V Scholar Plus Award- extended funding for exceptional V Scholars
Kidney cancer is the 8th most common cancer in the USA. Clear cell renal cell carcinoma (ccRCC) is the most common and lethal type of kidney cancer. If ccRCC spreads from the kidney, it becomes incredibly deadly. In addition, the drugs that successfully treat other cancers have no effect on the tumors. The most common gene mutation in ccRCC was discovered over 20 years ago. Figuring out the function of this gene led to the first drugs that successfully treat ccRCC. While this has improved the outcome for ccRCC patients, they still only survive an average of 22 months. Additionally, some patients do not respond to these drugs at all. We need to better understand what makes ccRCC different than other cancers. In addition, we need to understand what makes some ccRCC patients different than other ccRCC patients. Our lab studies a protein called Polybromo-1, which is the second most commonly mutated gene in ccRCC. Our goal is to understand how ccRCC patients with mutations in this gene are unique. From this information, we will figure out how to treat this set of patients using new drugs.
Clinical research is one of the most important ways that we learn what the best treatments are for patients with cancer. Clinical research often tests new types of treatment or new procedures, with the hope that more patients will benefit from the new treatment. Benefits can include improved chances of responding to therapy, fewer side effects and or safer treatments, and most importantly, in some cases, a better chance for cure.
Unfortunately, some groups of patients do not participate in clinical trials. This lack of participation may be due to obstacles or barriers to participation. Barriers can include difficulty in understanding cancer clinical trials or fear of participation in any type of experimental treatment.
The goal of our research project is to develop a better understanding of what barriers may exist in our community (the Greater New Orleans Region) and to develop educational programs to address concerns that some patients may have. We plan to develop a set of educational materials and create opportunities for community education which utilizes both printed materials and live community interactive educational activities.
These actions, if successful, will lead to a greater understanding of cancer clinical trials in cancer and potentially enhance the participation of minority and underrepresented groups in cancer clinical trials.
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