ME3BP-7 is a targeted cytotoxic agent that rapidly kills pancreatic cancer cells expressing high levels of monocarboxylate transporter MCT1

Nearly 30% of pancreatic ductal adenocarcinomas (PDACs) exhibit a marked overexpression of monocarboxylate transporter 1 (MCT1) offering a unique opportunity for therapy. However, biochemical inhibitors of MCT1 have proven unsuccessful in clinical trials. In this study, we present an alternative app...

Full description

Saved in:
Bibliographic Details
Main Authors: Jordina Rincon-Torroella, Marco Dal Molin, Brian Mog, Gyuri Han, Evangeline Watson, Nicolas Wyhs, Shun Ishiyama, Taha Ahmedna, Il Minn, Nilofer Azad, Chetan Bettegowda, Nickolas Papadopoulos, Kenneth W Kinzler, Shibin Zhou, Bert Vogelstein, Kathleen Gabrielson, Surojit Sur
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2025-05-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/94488
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Nearly 30% of pancreatic ductal adenocarcinomas (PDACs) exhibit a marked overexpression of monocarboxylate transporter 1 (MCT1) offering a unique opportunity for therapy. However, biochemical inhibitors of MCT1 have proven unsuccessful in clinical trials. In this study, we present an alternative approach using 3-bromopyruvate (3BP) to target MCT1 overexpressing PDACs. 3BP is a cytotoxic agent that is known to be transported into cells via MCT1, but its clinical usefulness has been hampered by difficulties in delivering the drug systemically. We describe here a novel microencapsulated formulation of 3BP (ME3BP-7), which is effective against a variety of PDAC cells in vitro and remains stable in serum. Furthermore, systemically administered ME3BP-7 significantly reduces pancreatic cancer growth and metastatic spread in multiple orthotopic models of pancreatic cancer with manageable toxicity. ME3BP-7 is, therefore, a prototype of a promising new drug, in which the targeting moiety and the cytotoxic moiety are both contained within the same single small molecule.
ISSN:2050-084X