Funded in partnership with the Lung Cancer Initiative of North Carolina, utilizing Stuart Scott Memorial Cancer Fund matching funds
Lung cancer causes more deaths than the next three cancers combined, and small cell lung cancer (SCLC) is the most aggressive type. Lung cancer disproportionally affects African Americans. Existing therapies prolong life, but only by months, and at the cost of substantial side effects. Within the immune system, T cells are particularly important for fighting cancer, but in patients with SCLC, neither the native immune system alone, nor with augmentation with existing immunotherapy, controls cancer durably. CAR-T is an exciting new technology that modifies a patient’s own T cells to recognize and attack cancer cells that bare a particular marker. This technology has revolutionized the care of some lymphomas and leukemias, including cures.
We have made a CAR-T for the treatment of Glioblastoma Multiforme because it bears a particular marker, GD2. 60% of SCLC also has GD2 and so we hypothesize that for these patients, GD2-directed CAR-T could provide dramatic tumor regression. Our cancer center has committed funding to a clinical trial if we can provide the necessary data to support it. More specifically, we would like to treat animal models of human SCLC with the proposed therapy to see if it is safe and effective. We would study where the CAR-T cells go and how well they kill cancer cells. The CAR-T contains a safety switch in case of side effects; we would test to make sure that it works. During the resulting human trial, we also seek funding to assess where the T cells go.
Black Americans often do not take part in research. They also have more aggressive breast cancer and a higher death rate from breast cancer. Overall, clinical trials have led to better outcomes for patients with breast cancer. However, the lack of Black Americans in clinical trials may be one explanation for higher death rates because new treatments are not tested in their aggressive cancers. Our goal is to help the community learn more about the role of research in breast cancer, and the value of taking part in that research. We will work with trusted members of the Black American community through our partners and lay Community Ambassador (CA) program to plan three forums. At these forums, community members will be able to talk with our doctors, clinical research coordinators, and CAs to learn about breast cancer, clinical trials, and what it means to take part in research. The forums will focus on breast cancer research. They will include questions from a host as well as questions from the audience. This will allow for an open discussion about breast cancer research. The goal of the forums will be to raise participants’ knowledge about research, and increase their odds of taking part in research.
Only a small percentage of patients with cancer in the US enroll on to clinical trials. This is creating a bottleneck for the development of new treatments. Efforts to improve how patients are identified for clinical trials are important to overcome this problem. One such effort which is showing promise is to use an individual known as a “pre-screener” to aid the clinical team in identifying eligible patients. The pre-screener functions as an extra set of eyes to review information generated from our electronic medical record as their records come in from referring physicians. They will be trained to look for patients meeting certain eligibility criteria and then notify the clinical team about the matches ahead of their visit. This will allow the team to better prepare and notify the coordinator for the study to be available at that time. The pre-screener will also serve as a resource for patients using our clinical trial education center in the clinic waiting area to help them navigate through the available information to identify a potential trial option to discuss with their physician during their visit.
The reasons why cancer patients do or do not participate in cancer (clinical trials) research are complex. Often this is due to the lack of awareness of which studies are occurring by both the patient and their primary care clinicians. Another very important reason is that patients, especially patients that do not speak English, are not invited to participate because the research team does not have non-English speakers or study materials in the patient’s language. We at the UC San Diego Moores Cancer Center (MCC) have the opportunity to better understand and address low clinical trials participation among our largest under-represented racial/ethnic group, Hispanics. Working with a multidisciplinary team of physicians and non-physician scientists, we propose to 1.) Educate community providers about breast cancer trials at MCC, and 2.) Assess specific interests and needs among the MCC breast cancer team, and combine this with existing evidence, including interview findings (knowledge and Hispanic from a recent (2016) V Foundation grant), to develop and implement minority clinical trial accrual training for the MCC breast cancer team. By focusing on minority breast cancer patients, V Foundation funds complement and expand our emerging efforts to increase minority clinical trials enrollment (accrual) and related outreach and inform how to intervene with MCC patients, providers, and leadership. We are particularly interested in targeting Hispanic breast cancer patients because they are the largest minority group in San Diego County, the region served by the MCC.
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.
Funded in partnership with WWE in honor of Connor’s Cure
Medulloblastoma is the most common malignant brain tumor in children. There are four distinct forms of this tumor based on its gene profiles, and a form known as Group 3 medulloblastoma is the most aggressive and deadly, which accounts for 25%-30% of all medulloblastoma. Each medulloblastoma group has distinct abnormal gene expression that determines how it creates, grows, and spreads tumors. Changes in gene behavior, like overexpression or underexpression, are controlled by what is called epigenetics. Fortunately, we know how to manipulate epigenetics with drugs. Dr. Hu and his colleagues found two epigenetic components that play important roles in controlling gene expression in tumor. Interestingly, these two epigenetic components seem to work together: when one component is suppressed, the other increases, and vice versa. A gene called MYC is very active in many cancers including Group 3 medulloblastoma. In this project, Dr. Hu’s team will characterize these two epigenetic components to understand more precisely how they work, particular in controlling MYC expression, even further, they will test in the lab whether “drugging” these epigenetic factors can halt the growth and spread of medulloblastoma tumors. If this hypothesis is proven, it may be possible to use these drugs in combination to treat this devastating childhood cancer.
The goal of “Campaign to Improve Access to Clinical Trials” at The University of Arizona Cancer Center (UACC) is to increase the clinical trial access to a diverse population in Arizona. Dr. Pavani Chalasani, Breast Cancer Disease Oriented Team Leader, will oversee the campaign to improves access by involving the breast multidisciplinary team, patient navigators and physician liaisons to develop educational materials and outreach programs. Patients and community physicians will be targeted through proposed outreach programs by developing targeted educational materials. Materials and training will be provided to introduce and educate about clinical trials to patients early by various members of their cancer team. The goal of this campaign is to become a model for other disease teams and cancer centers to implement to improve clinical trial enrollment.
First year of this Vintner Grant funded by the 2018 V Foundation Wine Celebration in honor of Robin Lail
Triple negative breast cancer (TNBC) is breast cancer that lacks HER2 and ER/PR receptors. Because most treatments are based on having these markers, TNBC is hard to treat. Additionally, TNBC often spreads to the brain (brain metastasis), which is even harder to treat. Radiation therapy (RT) is a standard local therapy for TNBC brain metastases; however, survival is less than 6 months.
Immune cells (found throughout the body) fight invaders like viruses, bacteria and cancer. However, cancer cells are highly adept at hiding from immune cells. Immunotherapies are being tested to help immune cells fight cancer better. There have been promising results using immunotherapies to treat brain metastases. We have shown that TNBC brain metastases have a higher number of immune cells called tumor infiltrating lymphocytes (TILs) compared to TNBC in breasts. More importantly, we found that patients with a higher number of TILs in their brain metastases live longer. Adding RT to immunotherapies can help immune cells to fight cancer. We will use mouse models to test this strategy, which will lead to a clinical trial in humans. We expect immunotherapy will also treat cancer inside and outside of the brain at the same time, which will improve the lives of patients facing this disease. We also want to find more signals in brain metastases (biomarkers) that will guide selection of the right immunotherapy for each patient. New biomarkers will help us treat the right patient, at the right time, in the right way, with immunotherapies.
Although significant progress has been made treating melanoma and the recent approval of several drugs for the treatment of advanced disease, several challenges remain. For example, clinical responses are generally short-lived as tumors quickly become drug resistant and patients relapse. Moreover, tumors can develop drug resistance through a diverse number of molecular mechanisms, making the development of second-line therapies extremely daunting. Therefore, it is critical to identify therapeutic targets that are common to the majority of resistant tumors. We have recently found that a protein kinase called S6K is activated in melanomas resistant to BRAF and MEK inhibitors. Moreover, we showed that inhibition of this protein using a triple drug combination blocked the growth of resistant tumors. This provides strong rationale for establishing S6K as a novel target for melanoma therapy. Notably, S6K is a common node for most resistance pathways. We propose to investigate the role of S6K in melanoma and determine the therapeutic value of targeting this protein. Towards these goals we will determine the consequences of blocking S6K in melanoma, identify the proteins that are regulated by S6K and use this knowledge to delineate combinatorial approaches that can lead to long-term tumor remission in a large number of melanomas, including those resistant to BRAF and MEK inhibitors. We expect that the data generated by these studies can be quickly translated into new strategies aimed at maximizing the therapeutic efficacy of MAPK inhibitors in melanoma and provide actionable information that will guide the design of future clinical trials.
Co-funded with Carousel of Possible Dreams/Friends of Cathryn and the Dick Vitale Gala
Only 45% of children with high-risk neuroblastoma are cured. The New Approaches to Neuroblastoma Therapy (NANT) consortium links laboratory and clinical investigators to develop therapies with high potential for improving survival and performs the first testing of them at 13 neuroblastoma centers. We propose new clinical trials for patients with resistant or recurrent disease that aim to 1) improve immunotherapy; 2) improve chemotherapy by targeting key drivers of the disease; and 3) improve measurement of response and prediction of outcome with a “biomarker” test for blood and bone marrow. We anticipate that these innovative studies will improve survival for children with high risk neuroblastoma.
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