Détail du document
Identifiant
oai:pubmedcentral.nih.gov:1040...
Sujet
ArticleAuteur
Rincon-Torroella, Jordina Molin, Marco Dal Mog, Brian Han, Gyuri Watson, Evangeline Wyhs, Nicolas Ishiyama, Shun Ahmedna, Taha Minn, Il Azad, Nilofer S. Bettegowda, Chetan Papadopoulos, Nickolas Kinzler, Kenneth W. Zhou, Shibin Vogelstein, Bert Gabrielson, Kathleen Sur, SurojitLangue
enEditeur
Cold Spring Harbor Laboratory
Catégorie
biorxiv
Année
2023
Date de référencement
09/08/2023
Mots clés
me3bp-7 mct1 cancer pancreaticRésumé
Nearly 30% of Pancreatic ductal adenocarcinoma (PDAC)s 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), that 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.
ONE SENTENCE SUMMARY: ME3BP-7 is a novel formulation of 3BP that resists serum degradation and rapidly kills pancreatic cancer cells expressing high levels of MCT1 with tolerable toxicity in mice.
Rincon-Torroella, Jordina,Molin, Marco Dal,Mog, Brian,Han, Gyuri,Watson, Evangeline,Wyhs, Nicolas,Ishiyama, Shun,Ahmedna, Taha,Minn, Il,Azad, Nilofer S.,Bettegowda, Chetan,Papadopoulos, Nickolas,Kinzler, Kenneth W.,Zhou, Shibin,Vogelstein, Bert,Gabrielson, Kathleen,Sur, Surojit, 2023, ME3BP-7 is a targeted cytotoxic agent that rapidly kills pancreatic cancer cells expressing high levels of monocarboxylate transporter MCT1 , Cold Spring Harbor Laboratory
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