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Molecular Cancer
Published in: Molecular Cancer 1/2010

Open Access 01-12-2010 | Research

The novel sigma-2 receptor ligand SW43 stabilizes pancreas cancer progression in combination with gemcitabine

Authors: John R Hornick, Jinbin Xu, Suwanna Vangveravong, Zhude Tu, Jonathan B Mitchem, Dirk Spitzer, Peter Goedegebuure, Robert H Mach, William G Hawkins

Published in: Molecular Cancer | Issue 1/2010

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Abstract

Background

Sigma-2 receptors are over-expressed in proliferating cancer cells, making an attractive target for the targeted treatment of pancreatic cancer. In this study, we investigated the role of the novel sigma-2 receptor ligand SW43 to induce apoptosis and augment standard chemotherapy.

Results

The binding affinity for sigma-2 ligands is high in pancreas cancer, and they induce apoptosis with a rank order of SV119 < SW43 < SRM in vitro. Combining these compounds with gemcitabine further increased apoptosis and decreased viability. Our in vivo model showed that sigma-2 ligand treatment decreased tumor volume to the same extent as gemcitabine. However, SW43 combination treatment with gemcitabine was superior to the other compounds and resulted in stabilization of tumor volume during treatment, with minimal toxicities.

Conclusions

This study shows that the sigma-2 ligand SW43 has the greatest capacity to augment gemcitabine in a pre-clinical model of pancreas cancer and has provided us with the rationale to move this compound forward with clinical investigations for patients with pancreatic cancer.
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Metadata
Title
The novel sigma-2 receptor ligand SW43 stabilizes pancreas cancer progression in combination with gemcitabine
Authors
John R Hornick
Jinbin Xu
Suwanna Vangveravong
Zhude Tu
Jonathan B Mitchem
Dirk Spitzer
Peter Goedegebuure
Robert H Mach
William G Hawkins
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2010
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-9-298

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