This project aims to improve the enrollment of men with prostate cancer into studies that require specific changes in DNA in order to be eligible. The largest barrier to enrolling patients is obtaining information about their DNA. Current standards of practice do not have clear recommendations on when to test the DNA of men with prostate cancer. Insurance does not always cover the DNA testing needed to get this information. The University of Virginia has two research programs open that obtain DNA testing on men with prostate cancer. This grant will support the efforts of the Clinical Research Outreach Program at UVA to recruit men with prostate cancer into these research programs in order to obtain DNA testing on a greater number of men with prostate cancer.
Prostate cancer represents the second most common cancer in men and the fifth leading cause of death worldwide. African American men in the US are more likely to develop prostate cancer and more likely to develop aggressive types when compared to other races. Between 2012 and 2016, 179 out of 100,000 African American men compared to 104 out of 100,000 Caucasian men were diagnosed with prostate cancer African American men with prostate cancer have a 2.5-fold greater risk of death from the disease.
Racial disparities exist in many disease types, including cancer. The development of cancer and survival of the disease are likely to include many components, including later detection and treatment, genetic factors, differences in biology, and social factors. Participation in cancer clinical trials provides access to new therapies, including potentially life-saving experimental therapy in patients for whom options are limited and prognosis is poor. African American patients are underrepresented in clinical trials in general, and more specifically in prostate cancer trials. The aim of this project is to promote, facilitate, and foster participation of minorities (with special emphasis on the African American population) in ongoing and to-be-opened prostate cancer clinical trials at VCU Massey Cancer Center (MCC). This will be accomplished by identifying current barriers, by increasing awareness among patients and physicians about available opportunities offered by MCC, and by organizing a prostate cancer clinical trial team that will guide eligible patients through screening and clinical trial treatment.
Funded by the V Foundation’s Virginia Vine event, in honor of WWE Connor’s Cure
Drugs are needed to treat cancer. Clinical trials are done to make sure drugs are safe and effective. Individuals volunteer for clinical trials. In cancer clinical trials, the volunteers usually have cancer. Volunteers may also be young or old, male or female and rich or poor. The important thing is to get a mix of volunteers who are similar to the cancer patients who will take the drug. Not very many people participate in clinical trials. More white people participate than any other race. This means that we don’t always know whether drugs are safe and effective in all people. Also, we don’t know if people are getting equal opportunity to participate in clinical trials. This study will look whether patients at Inova Schar Cancer Institute know about clinical trials. This study will also develop a program to help make all people, no matter what race, aware of clinical trials.
Funded by the V Foundation’s Virginia Vine event, in honor of WWE Connor’s Cure
Cure rates for children with cancer are improving, but cancer still comes back for many kids after finishing therapy. When cancer comes back it is more difficult to cure, and new treatments are needed to help these patients. The best way to develop new treatments is to treat patients with new therapies while collecting detailed information about how they tolerate the treatment and if it gets rid of their cancer – this is called being treated on a clinical trial, a research study designed to learn about how new treatments work for patients. These studies that involve new treatments are usually only offered at large hospitals that are connected to medical schools, so many patients are sent away from their homes to receive these treatments. Others choose to stay closer to home and not receive the newest therapies for their cancer. Often, there are research studies closer to home than their doctors realize. Getting this information to the doctors in our region would help make sure patients receive the newest therapies for their cancers while staying close to home. This grant would allow us to travel to nearby medical practices to tell the doctors about the new therapies that we offer at UVA as part of clinical trials, especially treatments that are being developed that allow the patient’s own immune system fight their cancer (called “immunotherapy”). Spreading this information will hopefully increase the number of patients that are treated on these research studies, and help cure more kids of their cancer.
Funded by the V Foundation’s Virginia Vine event, in honor of WWE Connor’s Cure
Cancer in children is rare, accounting for less than 1% of all cancer cases in the USA. Clinical trials are used to determine the most effective and safest treatment for a disease and are commonly used in cancer treatment for children, adolescents, and young adults. The main reason that children are not enrolled on clinical trials is that there is not an open trial available. However, some nationally available trials could be opened faster when needed in local hospitals or cancer centers. Currently, the process is quite complicated and involves many steps. Our goal is to develop a “library” of available clinical trials that could be activated quickly on an as needed basis for children with rare tumors or with a cancer that does not respond to standard treatment. We will examine the barriers to rapid activation, educate the committees that are involved in clinical trial activation at our institution about the uniqueness of childhood cancer, and come up with a process for rapid clinical trial activation for childhood cancer at the Massey Cancer Center.
Funded by the V Foundation’s Virginia Vine event, in honor of WWE Connor’s Cure
Our grant aims to develop drugs for altered forms of the protein MLL which arise in pediatric leukemia. Patients with leukemia harboring altered forms of MLL have very poor survival, highlighting the need for new approaches to treat these patients. The altered MLL proteins are highly dependent on the ability of one part of the protein to bind to DNA. We are developing drugs to block this binding. Our initial results support that this approach could be highly effective for treating this type of leukemia. Since this is a new way to treat the leukemia, it has the potential to be more effective than currently used drugs as well as less toxic. In addition, since this is a very different approach from existing drugs, it is likely that combinations of this new drug with existing drugs will provide unique benefits.
Funded by the Hirsch Family and the Dick Vitale Gala in memory of Ann Hirsch
Diffuse intrinsic pontine glioma (DIPG) is a fatal brain tumor in children for which the only treatment is radiation and chemotherapy. Sadly, this only results in a temporary relief of the symptoms. Almost all children die of this brain tumor within one year of diagnosis. There is no cure for DIPG. Chimeric antigen receptor (CAR) T cells are a new kind of therapy that has been wildly successful in children with leukemia where there was no hope for a cure. A T cell is a type of immune cell in the body. With CAR T cell therapy, we permanently give the patient’s own T cells a new molecule that shows it how to target then kill the cancer. Dr. Lee was one of the first in the world to treat children with leukemia with CAR T cell therapy and is an expert on its side effects. It has saved many lives so far. Dr. Lee is now making a new CAR in the lab that will recognize and kill DIPG tumors. His approach will be unique because he will add in a way to make the therapy safer and more effective. Once he has made this new CAR, Dr. Lee will use the facilities at the University of Virginia to make DIPG-targeted CAR T cells for patients as part of a planned clinical trial.
Breast cancer is the most common type of cancer in women worldwide. Metastatic disease is incurable and causes 90% of breast cancer-related deaths. Current treatments for breast cancer help patients live longer, but they have no effect once the tumor is in the brain. Moreover, by prolonging survival they increase the risk of brain metastasis over time.
Primary breast tumors secrete factors that travel through the blood and facilitate seeding and growth of new distant tumors by inducing changes in the structure of other organs. The proposed research will look at how regulatory T (Treg) cells, a type of immune cells heavily present in primary tumors, support changes in the brain tissue that allow brain metastasis to develop. To model this, we will utilize genetically engineered mouse models and surgical manipulations like the ones occurring in human breast cancer patients to investigate how the presence of regulatory T cell affect brain metastasis formation over time. Specifically, we will assess the changes in cell composition and structure of the brain tissue before metastasis develops in mice with and without Treg cells. In addition, we will evaluate changes in blood circulating factors, and establish the requirement of cells from the bone marrow and specific cytokines for the remodeling of the brain. By learning more about what happens to the brain tissue before metastases form, we hope to improve our chances of developing therapeutic strategies to prevent them.
Alveolar rhabdomyosarcoma is one of the most common children tumors. No effective therapy is available for advanced disease. Poor understanding of the etiology of the tumor is partly responsible for the lack of advancement in treatment. We are using tumor-signature events to study the cell of origin for the disease. Our results may shed light on the development of the tumor, and potentially lead to better diagnostic and therapeutic tools.
Funded in partnership with St. Baldrick’s Foundation
Alveolar rhabdomyosarcoma is one of the most common children tumors. Traditional dogma is that a particular molecular event is unique to the tumor, like a “signature”. We recently found the same event in normal cells, with a physiological function. This discovery raises the possibility that the tumors initiated from the same cells that harbor this “signature” fusion during normal development. Like fingerprints at a crime scene, this molecular event is giving us clues about the process of tumorigenesis. We will figure out the meaning of this signature molecular in normal development and how its’ going awry will drive rhabdomyosarcoma. In addition, cells at the same development stages harbor several other fusions that are also present in alveolar rhabdomyosarcoma. One of the newly identified fusions led us to uncover a potential new oncogene, which drives the tumor. Our finding will not only lead to better understanding of the tumor, but also have the potential for uncovering new treatment for the disease.
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