Gene replacement strategies for cancer.
The strategy for the inactivation or replacement of cancer-causing genes is analogous to the classic concept of gene therapy for replacement of defective or nonfunctioning genes. The gene families implicated in carcinogenesis include dominant oncogenes and tumor suppressor genes. Regional administration of viral vectors expressing wildtype p53 and antisense K-ras prevents growth for tumors with the specific genetic lesions in orthotopic tumor models and mediates regression of large established tumors. These studies provide a rationale for a new clinical protocol recently approved by the United States National Institutes of Health (NIH) Recombinant DNA Advisory Committee and the Federal Drug Administration (FDA) to replace a defective p53 gene with intratumor injection of recombinant retrovirus expressing normal p53 and to inactivate mutant K-ras by expression of antisense K-ras mRNA. If these agents are efficacious, their lack of toxicity may provide a sufficiently high therapeutic index such that they could be used as an adjuvant to surgery to treat patients with earlier stages of cancer or as prevention for second primary cancers for individuals with genetic abnormalities in premalignant lesions. Although much research needs to be done, the possibility of specific gene targeting with a high therapeutic index makes this a promising area for investigation.
Roth
J A
JA
Department of Thoracic Surgery, University of Texas M.D. Anderson Cancer Center, Houston, USA.
D016147:Genes, Tumor Suppressor; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics; D011995:Recombination, Genetic; D012190:Retroviridae / Q000235:genetics
D012333:RNA, Messenger