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
Pancreatic cancer is a very aggressive disease. It is the 3rd leading cause of cancer deaths in the USA. Only 8% of patients who can undergo surgery will survive past five years. Late diagnosis and lack of good treatment options are some of the reasons for this outcome. Recent progress in cancer immune therapy showed effect in cancers such as relapsed leukemia and metastatic melanoma. Unfortunately, immune therapy was not effective in patients with pancreatic cancer. One explanation for this result is that pancreatic cancer blocks immune responses against cancer. Thus, understanding how cancer promotes immune suppression is vital to our ability to treat this deadly disease. Our initial work has revealed that B cells promote growth of pancreatic cancer and resistance to immunotherapy. However, it is not clear how B cells promote cancer growth, and how targeting these cells can benefit patients. We propose to understand how B cells function in pancreatic cancer. The goal of this research project is to find new targets that can block immune suppression in pancreatic cancer. Using both mouse models of pancreatic cancer and patient samples, we hope to identify B cell based targets in pancreatic cancer. We ultimately hope to translate our findings into effective therapies that may also work with existing immune therapy treatments.
Funded by the 2018 Victory Ride to Cure Cancer
African Americans have the highest percentage of new cancer cases in the United States and the worst outcomes. Some people die from cancers that can be prevented or treated, simply because they are not aware of all of the treatment options. Cancer care can be very difficult because many times a patient has more than one doctor who is part of their care team. This can be scary and may make some people choose not to get cancer treatment, even if they can be cured. Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) wants to make sure that everyone has access to the best cancer care possible. To meet that goal, we will engage an African American Patient navigator (AAPN) – someone who is from the community who can help people learn about cancer, how to prevent it, what screening is required and what treatments are available. If someone diagnosed with cancer comes to WFBCCC for treatment and needs assistance, the AAPN will meet with them and work to help remove any barriers to care. The AAPN will also talk about clinical research that may be recommended as part of a treatment plan. Cancer research may improve outcomes for them or it may provide information that can help improve treatments for the next generation of cancer patients. Since African Americans get cancer more often, it is important to make sure they are represented in studies that look at new treatments and supports for cancer patients.
Funded by the 2018 Victory Ride to Cure Cancer
Clinical trials are important to improve cancer treatments and survival. Very few people are treated on cancer clinical trials and an even small number of those treated on a trial are African American. One way to solve this problem is to use specially trained staff to help cancer patients better understand clinical trials. These staff are called patient navigators. In this project, we will use patient navigators, one who is African American, to teach and support patients asked to be in cancer clinical trials. These navigators will work as a team to make sure that all African Americans who receive care at the Cancer Center are considered for cancer clinical trials. They will teach patients about clinical trials. They will also help them better understand the hospital system and give advice to patients who live far away and don’t have a car or place to stay when they come to their appointments. They can connect patients to finance counselors, social workers and other helpful community
services. To understand if the project is a success, we will compare the total number of patients, by race, treated on cancer clinical trials before and after the project. We will also study why patients chose not to be on clinical trials even when they are eligible. This information will help us design new projects in the future.
Funded by the 2018 Victory Ride to Cure Cancer
There is a low number of people involved in clinical studies. This is a national problem. This problem plays a part in poor health for people with cancer. It is even more of a problem for people of color who do not take part in clinical studies at the same rate as whites for several reasons. Some of these reasons include fear and not knowing about clinical studies. Also, some current and past research studies did not tell people of color the truth about the study and caused high rates of sickness and death in some cases. These reasons play a role in some people deciding not to take part in a study. Some people of color are not involved with clinical studies because they were not asked. Research teams may not ask people of color due to bias that they may not be aware of or concerns about trust. Studies show that most people who take part in a study do so because they were asked. The main reason people do not enroll in clinical studies is because they were not asked and did not know anything about it.
Studies suggest there is a need to teach research teams how to build skills in working with people of color. There is a need to build trust between patients and clinical staff as well as learn ways to increase the number of people of color enrolled in studies. The Just Ask: Diversity in Clinical Research Training Program works with patients, the community, and research teams to build skills and increase the number of people of color in clinical studies.
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.
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.
Prostate cancer is currently the second leading cause of cancer death in men in USA. Although surgical intervention and other first-line therapies for prostate cancer have improved over the past decades, there is still no effective cure for patients suffering from advanced/recurrent disease. Prostate cancer, like other cancers, is a heterogeneous disease such that individualized/precision medicine is likely to benefit patients. Our data indicate that a subset of prostate cancer exhibits reduced expression of a protein (cGAS) known to be involved in the response of cells to viral or bacterial infection. Importantly, lower expression of cGAS is correlated with prostate cancer recurrence, suggesting that loss of cGAS reduces efficacy of therapy. Interestingly, low cGAS is associated with poor outcome in lung cancer as well. In this proposal, we present preliminary data strongly supporting novel tumor suppressor roles of cGAS in prostate cancer functioning in individual cancer cells. We will fully investigate the underlying regulatory mechanisms and biological effects of the loss of cGAS in prostate cancer, along with the initial exploration of therapeutic vulnerabilities associated with this dysregulated pathway. We are hopeful that our studies will enable new therapeutic options for prostate cancer patients, with potential relevance to a subset of lung cancer.
“Spirit of Jimmy V” Award funded by the Dick Vitale Gala in honor of Holly Rowe
Fusion-positive rhabdomyosarcoma is driven by a specific fusion gene called PAX3-FOXO1 that acts as a powerful cancer driver. Unfortunately, this fusion gene is not yet able to be targeted directly with drugs. In fact, clinical trials over the past several decades have failed to improve the 5-yr overall survival rate for patients with fusion-positive rhabdomyosarcoma, which remains <50% for all-comers and <10% when metastatic. Prior work from our laboratory revealed that the Hippo pathway, a signaling network that in development ordinarily regulates the growth of organs and tissues, is turned off by PAX3-FOXO1. With Hippo turned off, pro-growth signals are left unchecked and cells become stimulated to proliferative. One of the main signals that gets activated by silencing of Hippo is TAZ, which is a powerful co-activator of cancer-promoting genes. We have seen that TAZ promotes resistance to chemotherapy and regulates the rhabdomyosarcoma cancer stem cell population. Our current studies, which utilize a variety of molecular biology and biochemical approaches in several cell culture and mouse model systems, aim to determine mechanisms by which TAZ controls chemoresistance and stemness. Ultimately, we are seeking to find vulnerabilities within the TAZ/PAX3-FOXO1 axis that can be exploited as novel therapies.
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.
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