Genomic and Microenvironmental Determinants of Premalignant Progression in FAP Patients
Chrisina Curtis, PhD, MSc
RZ Cao Professor of Medicine, Genetics & Biomedical Data Science and Sr Vice Chair of Research, Department of Medicine, Stanford Medicine
Director AI and Cancer Genomics, Stanford Cancer Institute
Investigator, Chan Zuckerberg Biohub
Genomic and Microenvironmental Determinants of Premalignant Progression in FAP Patients
Familial adenomatous polyposis (FAP) is a rare inherited condition that greatly increases the risk of colorectal cancer (CRC). Nearly all patients with FAP will develop CRC if the colon is not surgically removed. This is caused by an inherited mutation in the APC gene, which normally helps control cell growth. When both copies of APC become inactive in colon tissue, small abnormal growths called adenomas can form, some of which may eventually progress to cancer.
Our research aims to understand why some precancerous changes in the colon progress to adenomas and cancer, while many others do not. We previously studied polyps from FAP patients and discovered that adenomas often arise from multiple cell lineages, not just a single mutated cell. Building on this work, we will study the earliest visible changes in colon tissue, known as aberrant crypt foci (ACFs). These microscopic lesions can contain abnormal cells, but most never progress further. By comparing ACFs that remain harmless with those that develop into adenomas, we hope to identify the key genetic and environmental triggers of progression.
We will investigate three main questions: (1) Do different inherited APC mutations change how quickly abnormal growths appear? (2) Which additional mutations drive the transition from ACFs to adenomas? (3) How do surrounding tissue and immune cells influence this process? By answering these questions, we aim to improve how CRC risk is predicted in FAP patients and to guide the development of preventive therapies that could stop adenomas before they form.
