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 Cancerjournal_title
Molecular cancerauthors
Hornick JR,Xu J,Vangveravong S,Tu Z,Mitchem JB,Spitzer D,Goedegebuure P,Mach RH,Hawkins WGdoi
10.1186/1476-4598-9-298subject
Has Abstractpub_date
2010-11-22 00:00:00pages
298issn
1476-4598pii
1476-4598-9-298journal_volume
9pub_type
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