The Southeastern American Indian Cancer Health Equity Partnership (SAICEP) is a team made up of three cancer centers in North Carolina. These centers are working together to help lower cancer rates in American Indian communities. This year, with help from the V Foundation, SAICEP is starting a new project for Native youth and young adults, ages 16 to 30. The goal is to lower the risk of cancer by focusing on three things: getting the HPV vaccine, staying safe in the sun, and stop the use of unsafe tobacco products. To do this, SAICEP will work with the North Carolina Native American Youth Organization (NCNAYO). They will choose and train Native youth to become health ambassadors. These ambassadors will share important health information in their communities. SAICEP will also go to Native events across the state to talk with people and hand out materials about cancer health. At the end of the project, they will ask the youth and others what they learned and how the project helped. This project will help more young Native people stay healthy and avoid cancer in the future. It also gives Native youth a chance to lead and help their own communities.
Acute Myelogenous Leukemia (AML) is a fast-growing cancer of the blood and is the most common type in adults. Unfortunately, current treatments often don’t work well, and many patients get sick again or die. That’s why new and better treatments are needed. In our research, we looked at a protein that is found in large amounts on the outside of leukemia cells. Our earlier studies showed that this protein is needed for the cancer to grow. Because it’s on the outside of the cell, we can try to block it using special tools called antibodies. These antibodies attach to the protein and stop it from working. Here, we propose to develop an antibody that is able to target the protein and stop the cancer cells from growing. If we are successful, we plan to test the antibody in patients who are newly diagnosed or who haven’t gotten better with current treatments. This new antibody treatment could be a powerful new way to help people with AML live longer and healthier lives.
Immunotherapy is a type of cancer treatment that helps the body’s immune system fight cancer. It has changed how we treat many cancers. But not all patients benefit from it. So, we need new ways to make this treatment work better. One area of interest is the gut microbiome. This is the group of trillions of bacteria that live in our gut. These bacteria can affect how the immune system works and how well immunotherapy works. Our research, and that of others, has shown that people who respond to immunotherapy have different gut bacteria than those who do not. Diet plays a big role in shaping the gut microbiome, as the bacteria in our gut eat what we eat. We have shown that diet is linked to how well people respond to immunotherapy. In mice, changing the diet changed both the gut bacteria and the response to treatment. Now, we are testing if diet changes can help patients who are starting immunotherapy. We want to see if we can improve their gut bacteria and boost their immune response through their diet. If this works, it could be a simple and low-cost way to help more people benefit from immunotherapy. We also found that a plant-based, high-fiber diet lowers certain bile acids in the body; these acids may weaken the patient’s immune response. In this study, we will test if these bile acids can be used as a marker of the extent to which the diet and treatment are working.
Women with excess body weight are more likely to get breast cancer than women with a healthy weight. The effect of excess body weight is especially harmful to women with a family history of breast cancer. Excess body weight can cause many harmful effects to cells. By limiting or reversing these changes, we may be able to prevent breast cancer. We think that exercise or weight loss can decrease the risk of breast cancer by reducing damage to cells. This is very important as it may provide options for women who decide not to get prevention surgery. In the future, we will apply what we have learned to a clinical trial.
Glioblastoma (GBM) is the deadliest adult brain cancer. Even with standard of care treatment, survival rates are low. A major challenge is that the brain’s protective barrier blocks most drugs. The tumor also weakens the immune system, making it harder for treatments to work. CAR-T cell therapy is a promising treatment that trains T cells, a special immune cell, to recognize and attack cancer cells. It works well in other cancers, but not GBM. Normally, T cells follow signals from proteins called chemokines and cytokines to locate and fight disease. However, GBM blocks these signals, stopping T cells from working properly. Our study will develop a new immune gene therapy using a harmless virus called AAV to help the immune system fight GBM. This therapy reprograms nearby brain cells (called astrocytes) to send signals that attract and activate immune cells, including CAR-T cells. Our gene therapy will deliver two key proteins: CXCL9 (which attracts T cells) and IL-2 (which helps them grow and stay active). This targeted approach ensures a steady immune response right at the tumor. We will combine this immune gene therapy with CAR-T cells to improve their ability to find, survive, and attack the tumor. Our research will study how AAV works in the brain, activates CAR-T cells, and which AAVs can be used in human clinical trials.
Cancer immunotherapy with checkpoint receptor inhibitors (ICIs) causes autoimmune side effects. These side effects occur in most patients treated with ICIs. These side effects are debilitating and difficult to treat. My goal is to find treatments for ICI side effects. I developed new mouse models where ICIs induce the same autoimmune side effects as in humans. I will use these models to understand why ICIs are toxic. I will also understand how to treat the side effects of ICIs.
Pancreatic cancer is one of the most difficult cancers to treat, with only about 1 in 10 patients living five years after diagnosis. New and more effective treatments are urgently needed. One promising option is CAR-T cell therapy, which uses a patient’s own immune cells to fight cancer. While this treatment works well in blood cancers, it has not been successful in solid tumors like pancreatic cancer. One major challenge is the environment around the tumor, which lacks nutrients and weakens the immune system. This makes it hard for immune cells to survive and do their job. Our research aims to solve this problem by using a single target to improve both the immune cells and the tumor environment. We have found that changing how immune cells use energy can help them stay stronger and last longer in the body. At the same time, targeting how cancer cells grow makes the tumor more vulnerable to attack. By combining these two strategies, we hope to improve how well CAR-T cells work against pancreatic cancer. With support from the V Foundation, we will test this approach in models of pancreatic cancer. If successful, this work could lead to better treatment options for people with pancreatic cancer and potentially other hard-to-treat cancers as well.
Lung cancer is the leading cause of cancer death worldwide and deeply affects many families. Twenty years ago, the discovery of mutations in the Epidermal Growth Factor Receptor (EGFR) gene and therapies that were effective for these tumors (targeted therapies) transformed the field and the lives of patients with this disease. This remarkable progress resulting from targeted therapies is countered by the fact that metastatic EGFR-driven lung cancer remains incurable due to the emergence of drug resistance. Therefore, there is an urgent need to improve treatment of EGFR-driven lung cancer so people live longer and ultimately cure the disease. Through our studies we have found new possible drug targets in this disease. In this proposal, we plan to understand whether these are new targets and how they work. We will also test drugs that have been developed against these targets in mouse and human models of EGFR-driven lung cancer. These studies will allow us to develop the foundation for designing a clinical trial for patients with EGFR-driven lung cancer with the goal of finding better ways of preventing and/or overcoming drug resistance and improving and extending the lives of people living with this disease.
We aim to stop suffering and deaths from ovarian cancer. Therefore, we will explore how to improve the immune system’s ability to fight cancer. Cancer forms when normal cells change and grow wildly. The immune system can destroy abnormal cells. But cancer cells often evade immune system attacks. Ovarian cancer is a challenge. Only 10% of patients improve or survive with current treatments that help the immune system fight cancer. We study immune cells (B cells) and “neighborhoods” (tertiary lymphoid structures, or TLS) where these cells live. TLS can organize immune cells to fight cancer, and we investigate factors in ovarian cancer that impact TLS. We will test how immune cells (B cells) and non-immune cells (stromal cells) affect TLS creation and function. Our studies will show new ways to fight ovarian cancer. We will develop and lead new clinical trials. We will be poised to test a treatment for patients within five years that could change lives.
The number of melanoma cases in the United States continues to rise. When melanoma spreads to other organs, it is very deadly. Patients with this disease are usually first treated with medicines that help the immune system fight the cancer. This treatment works well for some people, but many can’t take the drugs because they have too many side-effects or simply do not work. For others, the medicines shrink the melanomas at first, but then they grow back. When immune medicines stop working, people with some kinds of melanomas can take other medicines(targeted drugs). However, targeted drugs do not work for a type of melanoma called NRAS mutant, which is very deadly and hard to treat. We found that a medicine used to treat leukemia may help targeted drugs work better for patients with this type of melanoma. In this proposal, we will learn how and why the leukemia medicine helps the targeted drugs work. We also will test our FDA-approved leukemia drug together with two different targeted drugs in mice. If the drugs work together to shrink the melanomas, then, in the future, we will test the treatment in patients by starting a clinical trial. Through this work, our goal is to give these patients more time to spend with their families, and eventually find a cure for this terrible disease.
