Maayan Levy, PH.D.
Project Title
Designing Metabolite-Based Prevention in Lynch Syndrome
Named Award
Stohlman Family Grant in memory of Richard Stohlman and Margaret Weigand
Position
Researcher
Institution
Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa.
My “Why”
Developing novel strategies for the prevention of colorectal cancer (CRC) is a pressing challenge. Screening by colonoscopy remains the most important and cost-effective strategy in reducing the incidence and mortality of CRC, as treatments have significant side effects. This is particularly the case in Lynch syndrome, an inherited disorder characterized by mutations in DNA repair genes. Patients with Lynch syndrome are predisposed to the development of cancer, including an increased risk for CRC.
My Mission
Even though there is a genetic predisposition to CRC, the age of onset and rate of progression is highly variable among patients, indicating that there is a strong environmental contribution to the development of CRC. This suggests that there is an urgent need to understand the critical role for modifiable environmental factors, including diet, in disease manifestation.
Research Overview
CRC is one of the most diagnosed and deadliest forms of cancer worldwide. Only a minority of CRC cases are related to a known genetic predisposition, and it is known to have a strong environmental component contributing to its molecular etiology, highlighting a critical role for adjustable behavioral practices that could be modified to support CRC prevention.
CRC incidence is associated with specific dietary patterns, but little is known about diets that promote the prevention or treatment CRC. Therefore, optimizing nutrition for the prevention and therapy of CRC is an urgent goal. This is particularly apparent in Lynch syndrome, where genetic predisposition and lifestyle jointly determine the rate of cancer initiation and progression in the intestine. While the genetic component awaits the development of effective gene therapy approaches, lifestyle interventions that prevent or delay the onset of tumor development are highly attractive for their low cost, non-invasiveness, low toxicity and their ability to combine with existing treatment strategies.
We have recently discovered a new dietary approach for the prevention and treatment of CRC (Dmitrieva-Posocco et al., Nature, 2022). We propose to apply this new knowledge to achieve a better basic understanding of the factors regulating the molecular etiology of CRC in Lynch Syndrome patients. This study may pave the way for a new metabolite-based adjunctive therapy for CRC.
Why Funding Matters
The Prevent Cancer Foundation funding will allow me to conduct research on developing novel strategies for the prevention of colorectal cancer. This study will serve as the stepping-stone for larger follow-up trial in individuals with Lynch syndrome and beyond. If effective, this study will establish a new a low-cost and widely accessible prevention for colorectal cancer.
My Hope
My hope is that by exploring the concept of using a single metabolite for the prevention of CRC, we will find a new intervention to prevent or delay the growth of colorectal tumors in individuals with a strong cancer predisposition, such as Lynch syndrome patients, and significantly improve their lives.