IGF::OT::IGF SBIR PHASE I, TOPIC 351: IMPROVING TARGETED CANCER THERAPIES BY MODULATING THE INTESTINAL MICROBIOME

Symberix, Inc., Durham NC

Investigators

Abstract

A sugar-scavenging bacterial enzyme (?-glucuronidase, bGUS) in the GI microbiome is responsible for the dangerous diarrheal side-effects of irinotecan, an anti-neoplastic agent used to treat advanced colorectal and pancreatic cancers. Irinotecan, which is rendered inactive in the liver by the attachment of a glucuronide sugar, is ?reactivated? by bGUS-mediated cleavage of the glucuronide sugar in the lower GI microflora. Reactivated irinotecan is highly toxic and damages nearby intestinal cells, resulting in intense, dose-limiting diarrhea. The goal of this project is to determine if bacterial bGUS?which exists as a number of different enzyme orthologues in the GI microbiome?is also involved in severe diarrheal side-effects associated with another class of anti-cancer drugs: tyrosine kinase inhibitors (TKIs).