OATP2B1 Deficiency Ameliorates Irinotecan-Induced Gastrointestinal Toxicity.

ABSTRACT: Irinotecan (CPT-11) is a prodrug of the topoisomerase I inhibitor SN-38 used in the treatment of metastatic carcinomas of the colon or rectum. The clinical utility of this drug is hindered by debilitating side effects, most notably, severe gastrointestinal toxicity, which affects up to 40% of patients. Although the accumulation of SN-38 in intestinal enterocytes, following biliary secretion and microbial metabolism of its glucuronide metabolite, is believed to be a critical preceding event to CPT-11-induced toxicity, the transport mechanism involved in this process remains incompletely understood. Here, we tested the hypothesis that the organic anion transporting polypeptide OATP2B1 is an intestinal uptake transporter of SN-38 and a critical determinant of CPT-11-induced toxicity. Mice wit

SUBMITTER: Taheri H 

PROVIDER: S-EPMC12748065 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature