Designed to identify, retain and further the careers of talented young investigators. Provides funds directly to scientists developing their own independent laboratory research projects. These grants enable talented young scientists to establish their laboratories and gain a competitive edge necessary to earn additional funding from other sources. The V Scholars determine how to best use the funds in their research projects. The grants are $200,000, two-year commitments.
Cancer treatments often fail to produce durable responses and resistant tumors eventually regrow. This process presents a major clinical challenge and results in significant patient mortality. The molecular details of this process, termed acquired resistance,are poorly understood and there are currently no therapeutic options to prevent it. For cancer immunotherapy, acquired resistance is emerging as a prevalent phenomenon affecting approximately half of patients who initially respond to treatment. Key to this process are the leftover tumor cells which remain alive and seed resistant tumors. We have observed a small subpopulation of cancer cells which survive directcytotoxic T cell attack over prolonged time periods. These cells, termed persister cells, survive through unknown mechanisms. In this proposal we will determine how persister cells survive despite undergoing T cell attackand also how a subset of persister cells eventually regrow and exhibit overt T cell resistance. If successful, our proposed work will shed light on acquired resistance to immunotherapy and may reveal new approaches to prevent tumors from recurring.
Pancreatic cancer will soon become the second biggest cause of death from cancer in the United States. Patients usually find out they have this disease after it is too late for surgery. This leaves treatment as the only option, and the ones in use only help patients live for a few months. To change this, we need to find new approaches to improve the survival of our patients.
Pancreatic cancer is hard to treat for many reasons. A key issue is that the tumors are made up of many cell types, not just cancer cells. Over the past few years, we have found ways these different cells can act together within a tumor to help cancers grow or avoid therapy. Most recently, we discovered that cancer growth can be slowed by blocking exchange of the amino acid asparagine when their mitochondria are stressed.
The goal of this project is to show how cancer cells make and share asparagine. Knowing this, we can better target this metabolism to kill the cancer cells. From our previous work, we also predict this strategy will help patients better respond to immunotherapy. The results from this project will show us how to improve pancreatic cancer treatment and provide data we need to start new clinical trials.
Funded by Matthew Ishbia and the Dick Vitale Pediatric Cancer Research Fund
DNA contains the story book of each human, written in our genome. Sometimes a single letter changes the meaning of a word, such as better to bitter. Likewise, in some children a small DNA change encourages cancer to form and grow. In childhood sarcoma, we recently discovered that certain DNA changes in cancer-causing proteins lead to errors in the rest of the genome’s ability to remember its cellular purpose. We found this was happening by formation of large “super-clusters” at cancer-causing genes. The goal of our research is to discover why and how these super-clusters form. We will explore the super-clusters using leading edge technologies including 3-dimensional genomic modeling, chemistry, cancer biology, and drug development focused on a deadly form of childhood cancer, called rhabdomyosarcoma. We anticipate finding that the super-clusters are integral to rhabdomyosarcoma progression; and our work will illuminate potential new treatment targets and routes, based on modifying the genetic error that is causing the cancer. For example, if we develop drugs that stop the formation of the super-clusters, will we also selectively kill the cancer cells? This new work will provide the scientific data to support a new class of therapies for children with these deadly cancers.
The immune system is our body’s defense against cancer and other threats. Recently developed drugs enable a patient’s immune system to attack cancer and potentially destroy it. These drugsthat enlist the immune system have revolutionized cancer treatment. However, despitesuccesses, not all patients respond to these exciting new drugs. Cancers that do not respond tothese drugs are known as “cold” tumors because they prevent an attack by immune cells. Thisbreakdown occurs because many cell types must communicate effectively with one another foran immune response against cancer to occur – cancer disrupts this process. We will test whetherimmune cells can be improved, such that they are resistant to the miscommunication that cancercauses. Normally, immune cells use signals to communicate with each other. Cancer eitherblocks these signals or replaces them with ones that are misleading. Our goal is to restore thesignals needed by immune cells so that they can mount an effective and sustained attack againstcancer. To realize this goal we have developed activators of these signals. We will determinewhich of these signal activators can protect immune cells from being misled or disabled bycancer. Our long-term goal is to improve cancer treatment options by developing these signalactivators into new therapies that allow a patient’s immune cells to attack a cold tumor.
Funded by Mark and Cindy Pentecost in memory of Chika Jeune
Pediatric brain tumors are the most common cause of cancer related death in children. Diffuse midline glioma (DMG), a type of childhood brain tumor, is universally fatal. Our lab has demonstrated in mouse models that DMG is responsive to two classes of treatments known as epigenetic and metabolic therapies. A major challenge in patients, however, is that single drugs are unlikely to be effective against this highly aggressive malignancy. Our grant proposal seeks to test the efficacy and biology of a combinatorial treatment of three drugs against DMG in an effort to generate pre-clinical data which could be potentially advanced to clinical trials in patients. In addition, our grant seeks to understand how these therapies influences the population of cells within a given tumor that may confer therapeutic resistance. We envision that these therapeutic and molecular insights will advance our understanding of DMG and lead to novel treatment paradigms.
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.
