Data from Reexpression of <i>Human Somatostatin Receptor Gene 2</i> Gene Mediated by Oncolytic Adenovirus Increases Antitumor Activity of Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand against Pancreatic Cancer

Abstract

<div>Abstract<p><b>Purpose:</b> Pancreatic cancer continues to pose an enormous challenge to clinicians and cancer scientists. Clinical studies show that tumor necrosis factor–related apoptosis- inducing ligand (<i>TRAIL</i>) exerts a potent and tumor-specific proapoptotic activity. However, most pancreatic cancer cells are resistant to <i>TRAIL</i> therapy. Human somatostatin receptor gene 2 (<i>hSSTr2</i>) is lost in 90% of pancreatic carcinoma. Oncolytic viruses are able to selectively lyse cancer cells and represent a promising novel anticancer therapy. Here, we investigated whether oncolytic adenovirus–mediated reexpression of <i>hSSTr2</i> would enhance <i>TRAIL</i>-induced antitumor efficacy against pancreatic cancer.</p><p><b>Experimental Design:</b> The antitumor efficacies of combined or single treatment of <i>hSSTr2</i> and <i>TRAIL</i> mediated by oncolytic adenovirus were compared in pancreatic cancer cell culture and xenografts. The mechanisms involved in <i>hSSTr2</i>-induced sensitization to <i>TRAIL</i> were studied.</p><p><b>Results:</b> Oncolytic adenovirus–mediated reexpression of <i>hSSTr2</i> potentiated <i>TRAIL</i>-induced tumor growth inhibition <i>in vitro</i> and <i>in vivo</i>. Reexpression of <i>hSSTr2</i> augmented <i>TRAIL</i>-induced apoptosis against pancreatic cancer cells via up-regulation of death receptor 4 and down-regulation of Bcl-2.</p><p><b>Conclusions:</b> <i>hSSTr2</i> restoration mediated by oncolytic adenovirus enhances <i>TRAIL</i>-induced antitumor efficacy against pancreatic cancer. Combined treatment with oncolytic adenovirus–mediated <i>hSSTr2</i> and <i>TRAIL</i> gene provides the rationale for a clinical trial in pancreatic cancer. (Clin Cancer Res 2009;15(16):5154–60)</p></div>