Deciphering the Mechanisms Underlying Dietary Protection from Colorectal Cancer
Abstract
I am an early-career scientist in cancer research. As an Assistant Professor at the University of Pennsylvania’s Perelman School of Medicine, I specialize in investigating colorectal cancer, one of the most common forms of cancer and one of the most frequent causes of cancer-associated mortality in the United States. My team has recently made a breakthrough discovery in the field of colorectal cancer. This finding described a new molecular pathway by which diets inhibit tumor growth in the gut. Specifically, my research group found that ketogenic diets, which are diets largely devoid of carbohydrates and rich in dietary fats, prevent the development of colorectal cancer in animal models and in human cancer cells. We now aim at understanding the mechanisms underlying this protective effect, in order to bring this discovery closer to application in patients. To this end, I have two major goals: (1) understanding the role of gut bacteria and immune cells in the tumors that mediate the impact of diet on intestinal tumor growth, and (2) build a network of collaborators, mentors, and peers who can support the next phase of research in this exciting field. Our goal is to involve patient communities in order to initiate an active exchange about the possibilities of using ketogenic diets and its metabolites in the prevention and treatment of colorectal cancer. I hope to become part of PRCRP’s Virtual Cancer Center in order to make actionable progress toward both goals. This proposal specifically addresses the following topic areas and challenges: FY22 PRCRP Topic Area: Colorectal Cancer FY22 PRCRP Military Health Focus Area: Environmental Exposure Risk Factors Associated with Cancer FY22 PRCRP Overarching Challenges: Prevention, Therapeutics Up to 2 million individuals are diagnosed with colorectal cancer each year. Screening for colorectal cancer remains the most important and cost-effective strategy in reducing the incidence and mortality of this disease, as treatment typically includes local excision by surgery, removal of nearby lymph nodes, chemotherapy, and radiation therapy – all of which have significant side effects. A new strategy that aides in the prevention and treatment of colorectal cancer development is thus urgently needed. We believe that diet is a powerful yet underutilized lifestyle element that can potentially support currently existing tools for screening and therapy. The subject of this research proposal is thus a central question in the prevention and treatment of cancer: What should we eat in order to minimize our risk of developing tumors? Our research will aim at identifying dietary patterns, metabolite supplementations, and the resultant signaling pathways in the body that have tumor-inhibitory effects in the gastrointestinal tract. This research needs to be carried out in a step-wise manner: (1) Identification of dietary patterns that are associated with inhibition of colorectal cancer in animal models and human cells. This part of the research program has been completed and recently published. (2) Deciphering of the mechanisms by which specific diets and diet-derived molecules prevent cancer. This research is subject of the current proposal. (3) Initiation of clinical trials to determine the safety and efficacy of dietary interventions or metabolite supplementation in at-risk populations. This step will depend on the results of the proposed project. This research will benefit everybody at risk of developing colorectal cancer. This encompasses essentially the entire population above the age of 50, since the risk for developing colorectal tumors increases with advanced age. There are also specific patient populations with an elevated risk for developing colorectal cancer. Among these populations are patients with Lynch Syndrome, an inherited disorder characterized by mutations in DNA repair genes. Patients with Lynch syndrome are predisposed to the development of
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310151
Entities
People
- Maayan Levy
Organizations
- United States Army
- University of Pennsylvania