The cancer-associated Sm-like oncogene: A novel target for the gene therapy of pancreatic cancer

Background. The prognosis for pancreatic cancer (PC) remains dismal, provid ing a clear need for the development of novel therapies. We have previously shown that the cancer-associated Sm-like (CaSm) oncogene is overexpressed in the great majority of pancreatic tumors and is required to maintain the transformed phenotype. The purpose of this study was to determine whether t he application of CaSm antisense gene therapy would generate a significant antitumor effect against PC. Methods. An adenoviral vector (Ad-alpha CaSm) expressing a 900-base pair an tisense RNA to CaSm was created. The PC cell lines AsPC-1 and Capan-1 were infected with this vector and examined for changes in in vitro proliferatio n by using methyl thiazol tetrazolium and soft agar assays. SCID-Bg mice be aring subcutaneous AsPC-1 tumors were treated with Ad-aCaSm (1 x 10(9) plaq ue-forming units) as a single intratumor injection with tumor growth and su rvival monitored. Results. AsPC-1 and Capan-1 cells showed decreased in vitro proliferation ( 93 %, P = .0041, and 70%, P = .0038, respectively) and anchorage independen t growth (55 %, P = .02 and 45 %, P = .03, respectively) after treatment. A d-alpha CaSm reduced in vivo AsPC-1 tumor growth by 40% (n = 10), extending median survival time from 35 to 60 days. Conclusions. Ad-alpha CaSm demonstrates a significant antitumor effect agai nst pancreatic cancer both in vitro and in vivo. These results support the role of CaSm as a significant gene involved in the neoplastic transformatio n of pancreatic tumors. Thus CaSm represents a novel gene target in PC and holds potential as a new treatment approach either alone or in combination with existing therapies.