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

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.

journal_name

Mol Cancer

journal_title

Molecular cancer

authors

Hornick JR,Xu J,Vangveravong S,Tu Z,Mitchem JB,Spitzer D,Goedegebuure P,Mach RH,Hawkins WG

doi

10.1186/1476-4598-9-298

subject

Has Abstract

pub_date

2010-11-22 00:00:00

pages

298

issn

1476-4598

pii

1476-4598-9-298

journal_volume

9

pub_type

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