In Vitro Evolution of Premalignant FAP Patient-Derived Organoids
Debra Van Egeren, PhD
A.P. Giannini Postdoctoral Fellow, Stanford University School of Medicine
In Vitro Evolution of Premalignant FAP Patient-Derived Organoids
Patients with familial adenomatous polyposis (FAP) develop hundreds to thousands of colorectal polyps. Understanding how these growths potentially develop into colorectal cancer will help us prevent this disease in individuals with FAP. To learn about this process, we will study how cells in these polyps acquire new abilities that cause them to turn into cancer. These new abilities can include cells being able to grow even when they receive signals to stop growing, or being able to invade nearby tissues or organs. We will examine polyps from FAP patients to see which individual cells have already developed these cancer-associated abilities by culturing these cells as organoids under conditions that only allow cells with these specific properties to survive. Additionally, we will continue to culture these patient-derived organoids in selection conditions that only allow survival of cells with these cancer-associated abilities to determine how and why they acquire this new capacity to develop cancer. Through DNA sequencing and other molecular profiling techniques, we will identify the mutations or other molecular changes that lead to cancer in these organoids. In the future, these causative mutations or molecular changes could be targeted by preventative strategies to reduce the risk of developing colorectal cancer in FAP patients.
