Unmet NeedFamilial adenomatous polyposis (FAP) is a hereditary condition caused by a mutation in the
APC tumor suppressor gene, with a reported incidence of 1 in 7,000 to 1 in 22,000 individuals. Patients with FAP develop thousands of colorectal polyps that will eventually become malignant, resulting in colorectal cancer later in life. The onset and frequency of these polyps vary within families that have the same
APC mutation, indicating that there are additional, unknown factors contributing to disease onset, which could include microbiome composition. An understanding of the microbiota associated with pre-cancerous lesions in hereditary colorectal cancer is needed and could lead to the identification of new therapeutic targets for the prevention of colorectal cancer and colectomy in FAP patients.
Technology OverviewJohns Hopkins researchers have identified the presence of a biofilm comprised primarily of enterotoxigenic
Bacteroides fragilis (ETBF) and/or psk+
Escherichia coli in the majority of patients with FAP who had colonic tumors. Murine modeling of the co-colonization of ETBF and psk+
E. coli also demonstrated that their virulence factors were responsible for tumor formation and enhanced bacterial adherence in the colon. These results indicate that of the trillions of bacteria in the colon microbiota, these two species can be sufficient to induce tumorigenesis, especially in patients with FAP. Targeting ETBF and psk+
E. coli in the colon and disrupting their mucosal adherence through a vaccine or another technology could delay onset of colon tumorigenesis and inevitable colectomy in FAP patients. Screening for these bacteria in non-FAP patients could also identify those with higher risk of colorectal cancer.
Stage of DevelopmentThe inventors have identified two bacterial strains in the colon microbiota of FAP patients that are associated with colon tumorigenesis. Targeting these bacterial strains at or soon after birth in FAP patients could represent a novel method of delaying or preventing colorectal cancer. The efficacy of this proposed therapeutic strategy will be evaluated in animal models and human patients.
PublicationDejea CM, et al.Science 2018 Feb 2; 359(6375):592-597
