Jr. Kelley et al., The cancer-associated Sm-like oncogene: A novel target for the gene therapy of pancreatic cancer, SURGERY, 128(2), 2000, pp. 353-360
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.