Chemoprevention in Familial Adenomatous Polyposis Through Menin Inhibition
Bryson Katona MD, PhD, AGAF, CGAF
Jeffery and Cynthia King Associate
Professor of Lynch Syndrome Research
Executive Director, King Center for Lynch Syndrome
Director, Gastrointestinal Cancer Genetics Program
Associate Professor of Medicine and Genetics
Division of Gastroenterology and Hepatology
University of Pennsylvania Perelman School of Medicine
Chemoprevention in Familial Adenomatous Polyposis Through Menin Inhibition
This grant proposal will explore whether targeting the protein menin may serve as a novel chemoprevention approach for FAP. We show that in mouse models of FAP where menin is not expressed, the mice develop a smaller polyp burden and have longer survival compared to FAP mice that express menin in their colons. To further these preliminary data findings, in this proposal we will determine the mechanism whereby menin is promoting colon polyp growth, and whether this is specific to FAP or may also be applicable to other polyposis syndromes. We will also test whether small molecule menin inhibitors, which are drugs that can be taken orally, can reduce growth of colon organoid models generated from patients with FAP and also reduce colon polyp development in FAP mice. If successful, this investigation may define a novel strategy for chemoprevention in FAP that could potentially reduce CRC risk and the need for frequent colonoscopy and/or preventive colon surgery in FAP patients.
