CES2 Expression in Pancreatic Adenocarcinoma Is Predictive of Response to Irinotecan and Is Associated With Type 2 Diabetes.

ABSTRACT:

Purpose

The combination chemotherapy of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) has provided clinically meaningful improvement for pancreatic ductal adenocarcinoma (PDAC). We previously uncovered a role for the serine hydrolase carboxylesterase 2 (CES2) in mediating intratumoral activation of the prodrug irinotecan, a constituent of FOLFIRINOX. We aimed to further test the predictive value of CES2 for response to irinotecan using patient-derived xenograft (PDX) models and to elucidate the determinants of CES2 expression and response to FOLFIRINOX treatment among patients with PDAC.

Methods

PDXs were engrafted subcutaneously into nude mice and treated for 4 weeks with either saline control or irinotecan. CES2 and hepatocyte nuclear factor 4 alpha (H

SUBMITTER: Capello M 

PROVIDER: S-EPMC10860959 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature