Funded in partnership with Miami Dolphins Foundation
Vitamins play an essential role in keeping our immune system healthy by maintaining normal blood cell production. Certain types of vitamins can also help in the prevention and treatment of blood cancers. Vitamin A has been used for decades to treat a subset of blood cancer patients with defects in a protein that relies on vitamin A for its normal activity. More recently, our work has shown that vitamin C can also stop blood cancers from forming, and slow cancer growth, by maintaining or restoring the activity of a protein known as TET2. Loss of TET2 function causes an increase in the growth of blood cells that drive cancer development. Mutations in TET2 that lower its activity are frequently found in patients with blood cancers. TET2 is also frequently defective in the blood cells of the healthy elderly population that can put them at a much greater risk of developing a blood cancer. The goal of our work is to understand how we can maintain TET2 activity to prevent and block cancers of the blood. Interestingly, vitamin A treatment can increase TET2 levels in cells, which in combination with vitamin C restores TET2 activity more than either treatment alone to stop the growth of blood cancer. Our goal in this study is to model combination treatment strategies of vitamin A and vitamin C to prevent blood cancer formation and growth that can be used as a potential therapy to treat blood cancer patients with a loss in TET2 activity.
Even if cancer therapeutics and cures were found, they may not benefit African Americans and other under-represented minorities, due in part to a lack of participation in clinical cancer trials and cancer disparities research. Los Angeles has the seventh largest population of Blacks in the United States. Although many may think this population is homogeneous, there are still differences among individuals who identify as Blacks in Los Angeles. This population includes not only individuals born in the U.S. of African ancestry, but also foreign-born including of African or Afro-Caribbean origin. If we are to truly achieve “Victory over Cancer”, under-represented minorities, including all segments of the African American community need to engage in the research process. This grant will allow for holding focus groups with various segments of the AA community, achieving a greater understanding of barriers to CT and acceptance of precision medicine research. We will be able to obtain information for the creation of an outreach and awareness raising tool kit to work with AA community leaders, faith based and other organizations, in advancing knowledge and changing attitudes towards CT participation, provision of biospecimens and inclusion of AA communities in cancer disparities research.
EMPOWERED U is a community research program to better understand and address the gaps in cancer research in our diverse communities. Black or African American (AA) patients have lower rates of joining cancer prevention or treatment clinical trials. For many cancers, Black or AA patients are still diagnosed later or may not live as long as white patients. Many factors such as insurance, poverty, age, other diseases, racism and bias in treatment, and trust of medical research due to prior racism may cause these differences. As science for cancer treatment advances, the gap will increase if not everyone has equal access to new technology. Patients may miss the chance to join new trials and researchers may miss the chance to better understand disease and treatments in diverse groups.
This program partners directly with community members to study opinions from patients, caregivers, local community leaders, and medical providers to better understand barriers, myths, fears as well as factors that can improve trials participation and the patient experience.
The patient and community voice will be captured in focus groups and interviews. The community research team will use this important input to design a Community Clinical Trials Toolkit (booklets, print cards and videos) to better answer questions and worries and support patients to learn about clinical trials. Importantly, we will also create community led education for providers and clinical research teams about community and patient perspectives and best practices to support patients.
With an extensive cohort of gastric cancer genomic data, there are many new avenues for translational research and clinical investigations. Importantly, a registry this size provides significant degree of statistical power, thus providing researchers with an invaluable resource. Researchers and clinicians in any discipline and at any institution across the world may access this data for independent discovery and validation studies. For example, an investigator may access the data to answer the question, “I found that H. pylori infected patients often have downstream functional mutation in the gene MUC1; can this finding be replicated in another patient population?” The end results may be a new practical and scalable early detection technology, or a precision therapy for gastric cancer patients. Ultimately, the GCR is designed to be a resource for accelerating gastric cancer research.
Funded by the 2019 Wine Celebration Fund a Need for Canine Comparative Oncology
Osteosarcoma (OS) is a common and devastating cancer of the bone which occurs in both dogs and humans. Upon diagnosis, the majority of dogs require amputation and chemotherapy. Despite this, most relapse within a year of diagnosis. In humans, OS is the most common bone tumor of adolescents and young adults (AYA). Pediatric and AYA patients with metastatic OS at diagnosis or who relapse after frontline therapy have an extraordinarily poor prognosis, with only a 20-30% survival at 5-years. Despite concerted attempts, these outcomes have not changed in >25 years.
Due to similarities in genetics, biologic behavior and treatment responses, canine OS is considered the best model of pediatric and AYA OS. We have used this model to investigate new immunotherapies and some of these have been translated into human trials (NCT03900793). In preliminary studies, we have determined that canine OS overexpress a protein known as B7-H3, which is absent in normal dog tissues (heart, liver, brain, kidney and spleen). We also find that both dog and human OS are infiltrated with tumor associated macrophage (TAM), which suppress immune responses to the tumor. The Dow lab has designed and tested methods to deplete these TAMs and the Verneris lab has been testing ways to target B7H3 using cellular immunotherapy with chimeric antigen receptors (CARs). Here, we will bring these two approaches together to test whether the improve outcomes in rodent xenograft models and in pet dogs with macroscopic pulmonary OS metastases in a clinical trial at CSU.
FUNDED BY THE STUART SCOTT MEMORIAL CANCER RESEARCH FUND
Ovarian cancer is adeadlydisease. A goal of ovarian cancer treatment is to find drugs that allow patients to live longer. The methods that predict whether these drugs workignore proteins. There is no information about how proteins affect survival. Also, it is not known how proteins contribute to harmful side effects. In this project, we will identifythe proteins that are involved in responding to a group of drugs named PARP inhibitors. These drugs are used to treat patients with the most deadly form of ovarian cancer. It is critical to identify the proteins associated with good PARP inhibitor response. This will help us to understand how PARP inhibitors have anti-cancer activity. As a result, it will be easier to identify the ovarian cancer patients who will respond to PARP inhibitor treatment. This research projectsupports the goal of the V Foundation, and it will help to accelerate victory over ovarian cancer.
FUNDED BY THE STUART SCOTT MEMORIAL CANCER RESEARCH FUND
Tobacco use, specifically cigarette smoking, is a primary reason that adults develop and die from lungcancer. Adults with low income smoke cigarettes at higher rates than the general population, but they areless likely to go to the doctor and receive help with quitting. It is important to design programs that reachthis population outside of a hospital or clinic setting.
Community health workers (CHWs) are frontline public health workers who work with these communitiesto help improve their health and connect them to medical services. CHWs are often the first, andsometimes the only, healthcare provider for these adults. Training CHWs on conducting briefinterventions for tobacco cessation, or quitting smoking, is important. However, current trainings fortobacco cessation are not always accessible to CHWs because of cost and time-constraints, andbecause the trainings are not relevant to CHWs’ patients’ experiences. This study will address theseissues by adapting a tobacco cessation training specifically for CHWs. We will use information thatCHWs have provided about their practices caring for their patients to make the training relevant to theirpatients’ experiences. We will then give the training to CHWs and test whether the training increasedCHWs’ knowledge about tobacco cessation, and whether the training is appropriate for CHWs and theirpatients. Having more CHWs trained in tobacco cessation will increase the number of adults who receivehelp to quit smoking, which will help to reduce tobacco use and, ultimately cancer, among adults with lowincome.
FUNDED BY THE STUART SCOTT MEMORIAL CANCER RESEARCH FUND WITH SUPPORT FROM BRISTOL MYERS SQUIBB
For a patient with a blood cancer that has not responded to standard treatment, an allogeneic hematopoietic cell transplant (allo-HCT; also referred to as bone marrow transplant) provides the potential for a cure. However, there is still the possibility that the patient’s disease may relapse. Another potential risk of allo-HCT may result when the immune cells from the bone marrow see the recipient as foreign, leading to a complication called graft versus host disease (GVHD). In this approach, I will investigate the use of an allo-HCT followed by donor immune cells targeted to kill the tumor, CD19-targeted chimeric antigen receptor (CAR) T cells. Additionally, to improve the safety of the donor T cells I will utilize genetic engineering with CRISPR/Cas9 to remove the T cell receptor. Hence, I will also evaluate the functional and mechanistic impact of this genome engineering on the immunometabolism of the T cells.
FUNDED BY THE STUART SCOTT MEMORIAL CANCER RESEARCH FUND WITH SUPPORT FROM BRISTOL MYERS SQUIBB
For the past 20 years, the number of people under the age of 50 who are diagnosed with colon and rectal cancer has been rising very quickly, especially among Latinos living in the US and in Mexico. In fact, it is predicted that in the next 10 years, 1 in 10 colon cancer cases, and 1 in 4 rectal cancer cases will be in people younger than the age of 50. Currently, very little is known about the reasons behind this. We think that the food we eat, and our behaviors may play a role in getting colon and rectal cancer. We also think that the type of bacteria in our gut may predispose certain people to getting cancer at a younger age.
In order to explore this, we plan to invite 90 people in California and Mexico City, who identify as Latino, and who were younger that 50 when they were diagnosed with colon or rectal cancer to participate in our study. We will ask them to collect one stool sample at home, and will study the bacteria in that sample as well their tumors. We will also collect detailed information about the foods they eat, and their background using surveys. Overall, we hope to gather very important information that could help us understand why colon and rectal cancer is on the rise among younger people. This information could also help us identify new ways of preventing colon and rectal cancer in the future.
FUNDED BY THE STUART SCOTT MEMORIAL CANCER RESEARCH FUND
Understanding young women’s breast cancer is a public health priority. In the UnitedStates, the rate of metastatic breast cancer is rising faster in women aged 25-39compared to older women.Pregnancy is associated with an increased risk of breast cancer for 10 years after birth.Being diagnosed with breast cancer during this period is called postpartum breast cancer(PPBC). PPBC tumors are often more life threatening. Also, while breastfeeding reducesbreast cancer risk, we do not know how breastfeeding impacts PPBC.Identifying unique tissue features within the PPBC tumor could lead to better outcomes.We will use the New York Breast Cancer Family Registry to analyze tumor tissue from150 women. 50 samples from women diagnosed with breast cancer less than 5 yearsfrom childbirth (PPBC cases). 50 samples from women diagnosed more than 10 yearsfrom childbirth. 50 samples from women diagnosed who have never given birth. We willstain the tumor tissue with four biological markers. These markers have been associatedwith the spread of breast cancer and death from breast cancer. Staining, or addingcoloring, to the tumor tissue will help identify unique features across the breast cancercases.
Aim 1: Identify unique features within the tumor samples using the four markers in150 cases.
Aim 2: Examine if the unique features predict breast cancer clinical features in 150cases.
We know little about the PPBC tumor tissue. Identifying unique tissue features that mapto the PPBC tumor can improve survival outcomes for young adult patients.
