Therapy of pancreatic cancer via an EphA2 receptor-targeted delivery of gemcitabine
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Bridget A. Quinn1,*, Si Wang2,*, Elisa Barile2,3, Swadesh K. Das1, Luni Emdad1, Devanand Sarkar1, Surya K. De2,3, Susan Kharagh Morvaridi4, John L. Stebbins2, Stephen J. Pandol4, Paul B. Fisher1,2, Maurizio Pellecchia2,3
1Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine and VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, USA
2Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037, USA
3Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, CA 92521, USA
4Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
*These authors contributed equally to this work
Paul B. Fisher, e-mail: firstname.lastname@example.org
Maurizio Pellecchia, e-mail: email@example.com
Keywords: 123B9, EphA2, targeted delivery, drug-conjugates, gemcitabine
Received: October 08, 2015 Accepted: January 29, 2016 Published: March 05, 2016
First line treatment for pancreatic cancer consists of surgical resection, if possible, and a subsequent course of chemotherapy using the nucleoside analogue gemcitabine. In some patients, an active transport mechanism allows gemcitabine to enter efficiently into the tumor cells, resulting in a significant clinical benefit. However, in most patients, low expression of gemcitabine transporters limits the efficacy of the drug to marginal levels, and patients need frequent administration of the drug at high doses, significantly increasing systemic drug toxicity. In this article we focus on a novel targeted delivery approach for gemcitabine consisting of conjugating the drug with an EphA2 targeting agent. We show that the EphA2 receptor is highly expressed in pancreatic cancers, and accordingly, the drug-conjugate is more effective than gemcitabine alone in targeting pancreatic tumors. Our preliminary observations suggest that this approach may provide a general benefit to pancreatic cancer patients and offers a comprehensive strategy for enhancing delivery of diverse therapeutic agents to a wide range of cancers overexpressing EphA2, thereby potentially reducing toxicity while enhancing therapeutic efficacy.
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