To understand how genes change in cancer, our field has uncovered many gene mutations and deletions in patient tumors. However, we have not yet been able to create treatments that can combat many of these changes. This research proposal will test the potential for new combinations of medicines to treat tumors with a common gene many cancers need on for survival, PRMT5. A number of aggressive tumor types have PRMT5 as a drug target including lung cancer which remains the leading cause of cancer-related deaths in the U.S. and pancreatic cancer where >90% of patients with this disease will succumb to it. We need to make better medicines to treat these cancers.
We will test our ability to drug PRMT5 protein in lung tumors in combination with other new drug targets. This work will provide fundamental insights into mechanisms of PRMT5 function and reveal new strategies to treat an aggressive and deadly form of cancer. It is necessary that we test and design effective, rationale combination therapies in cancer. These efforts aim to effectively kill tumors and to avoid tumors coming back in the patient.
This work could lead to clinical trials in the future that would directly benefit cancer patients and their families. My goal is for our laboratory to contribute to mentoring young scientists and to improving cancer treatment for patients. This V scholar award will help me to achieve my goals by providing additional support, mentorship, and scientific exchanges.
The immune system plays a crucial role in controlling cancer growth. Immunotherapies help fight cancer by boosting the body’s immune response against the tumor. However, many patients have tumors that either don’t respond or become resistant to these treatments. One reason for this resistance is that a type of immune cell called macrophages, which are found in the tumor, can shut down the immune response and stop it from killing cancer cells. Right now, we don’t have effective treatments to target these macrophages. Our research team has discovered a new weakness in these macrophages. By blocking a special protein they use, we can stop them from taking in folate (a type of vitamin), which leads to their death. We will use patient samples and a new mouse model we created to figure out why these macrophages need folate and how we can use this information to enhance the immune response against tumors. This could lead to new treatments that specifically kill macrophages in tumors, helping more cancer patients benefit from immunotherapy.
Funded by the V Foundation’s 30th Anniversary Gala Event
Pancreatic cancer is the 4th most common cause of cancer death in the United States with one of the worst survival rates of any cancer. Patients with pancreatic cancer struggle to find clinical trials given the lack of options, the lack of any promising findings, the lack of functionality to tolerate many trials. Our research directly impacts cancer patients providing an innovative and promising therapy that has had success in other cancers. Our clinical trial will study pancreatic cancer patients receiving treatment with their own immune cells that we will have taken from their blood, re-engineered the cells to fight their cancer, and injected their re-engineered immune cells back into their body.Our research will study the blood from these patients and look for markers that are associated with treatment response in similar clinical trials. We will also study their tumor tissue before and after treatment and look to see if the injected, re-engineered immune cells were able to travel to the tumor, grow and thrives and kill cancer cells.
Funded by the V Foundation’s 30th Anniversary Gala Event
There is a new kind of cancer treatment called immune checkpoint blockade (ICB) that helps the body fight cancer by making the immune system stronger. Doctors use ICB with chemotherapy to treat triple-negative breast cancer (TNBC), but it doesn’t always work for everyone, so we need to find better ways to help these patients.
Scientists are studying tiny living things called microorganisms, like bacteria, that live in and on our bodies. These microorganisms can help us stay healthy and fight diseases. New research suggests that the gut microbiome—the collection of microorganisms in the digestive tract—might influence how well these treatments work. Some types of bacteria can help people respond better to the ICB treatment because they release beneficial metabolites.
In this project, scientists want to see if probiotics (which are good bacteria) or the beneficial metabolites they make can make the cancer treatment work better. They will look at samples from patients before and after treatment to see if these good bacteria and metabolites are helping.
Funded by the V Foundation’s 30th Anniversary Gala Event
Despite its exciting impact, most cancer patients still do not benefit from immunotherapy. We have discovered a strategy used by cancers to avoid detection by the immune system. This work aims to use markers to determine which patients would be more likely to benefit from blocking this pathway in order to improve the effectiveness of immunotherapy. Using such a tailored approach is expected to enhance responses in a greater number of patients while avoiding the use and costs of ineffective therapies.
Funded by the V Foundation’s 30th Anniversary Gala Event
About half of all cancer patients will get radiation therapy (RT) as part of their treatment. But some cancers are naturally resistant to RT, and others become resistant over time. One idea to fight this resistance is to combine RT with treatments that boost the body’s immune response. In this project, we will test if a particular type of immunotherapy can overcome resistance to radiation and make RT work better. To check this idea, we’ll start by using lab mice to figure out the best way to do this treatment. These mouse tests will show us when to give the immunotherapy with RT for the best results. Once we know this, we’ll start a clinical trial with pet dogs that have cancer. The goals of this trial are to (1) prove that combining localized immunotherapy with standard RT is safe, and (2) show that this mix works better than just RT alone. The specific immunotherapy we’re looking at is called XCSgel-IL12. It’s a new type of treatment we made. It gets injected straight into the tumor, and it can be made in large amounts for a low cost. It looks very promising for beating radioresistance in many cancer types. This study will focus on soft tissue sarcoma. If it works well, we can start trials in humans with this type of cancer. It could also spark more research on combining RT with XCSgel-IL12 in other cancers in the future.
Every year, over 40,000 people are diagnosed rectal cancer in the US. Many of these patients will receive radiation treatment. Sadly, radiation does not cure all rectal cancers. Many non-genetic, or “epigenetic,” factors control how cancer cells are built and how they respond to treatment. Often, these factors mimic biology seen in normal, non-cancer cells. Radiation causes normal intestine cells to change into stem cells that repair damage. We suspect these radiation-induced stem cells also occur in rectal cancer. We propose to test whether these radiation-induced stem cells cause rectal cancer to resist radiation. We will also map out the epigenetic factors that allow these stem cells to arise. To do this we will use new methods we have developed to show the fine details of epigenetic regulation. From our data, we will discern new mechanisms of rectal cancer radiation response. We hope these studies will yield novel treatments to combine with radiation for rectal cancer.
African Americans have the highest percentage of new cancer cases in the U.S. but are less likely to be in research. People ages 13-39 partake in research less than any other age group. Hispanic patients also participate less if they do not speak the language or their culture is different, so they need different care. Patients from rural areas have a hard time getting to a cancer treatment center or need help figuring out the system once they are there. People without health insurance or poor insurance plans have access to care and research issues. AHWFBCCC wants to make sure everyone has access to the best cancer care possible. The best care possible may mean a patient joins a clinical trial. It is important to make sure all people are spoken for in studies that look at new treatments or supports for cancer patients. To meet that goal, we started a population health navigator program- people who are from the community who can help people learn about cancer, how to prevent it, what screening is needed and what treatments are available. If someone is diagnosed with cancer, the navigator will help to remove barriers to care and will talk with them about research as part of their care.
The low number of minority populations in clinical trials leads to higher mortality in these groups. It is important to address these inequities in order to address these cancer disparities. By developing a program that addresses the needs of patients, clinics, institution and communities, we hope to support minority patients seeking care at DCI to lower the barriers to accessing life-saving cancer clinical trials.
North Carolina (NC) has the largest American Indian (AI) population east of the Mississippi River. Yet, we do not know much about the health and health care of AIs in NC. We do know cancer is their number one cause of death. We need to better understand cancer and cancer-related needs in this group to reduce the burden of cancer. Three NC cancer centers joined together in 2021 to learn more about how to help AIs with cancer. We will study how cancer of the liver and stomach affects American Indians in NC. And we want to find and create resources for our AI community. First, we will use the NC Cancer Registry and health insurance files to learn more about how and where AIs in NC get cancer care and any potential disparities. We will then have a community event to test for and treat the top cause of stomach cancer. Lastly, we will educate about liver and stomach cancer to help prevent them. This work will help AIs in NC by showing what the greatest needs are and the opportunities for better care. The long-term goal is to improve cancer outcomes in all AIs.
