Antisense regulation of oncogenes in human cancer.
Gene transfer or manipulation of genes for the treatment of cancer is a rapidly expanding field. In recent years, much attention has been focused on manipulating cancer genes and applying antisense technology in therapeutic ways. Consequently, antisense RNA control is now recognized as a specific means of regulating gene expression at the posttranscriptional level. Defects in vital genes occur in many human diseases, including cancer, defects that may be due to an accumulation of mutations in the genes that leads to the production of faulty proteins. Although the biological significance of such mutant proteins still remains in question, recent experiments have demonstrated that genes overproducing faulty proteins are often associated with increased tumor cell growth. Moreover, using a stretch of antisense RNA to block the production of such defective proteins can effectively silence their genes; as a result, tumor cells stop dividing rapidly and revert to a more normal phenotype. Therefore, antisense RNA technology could have a significant impact on cancer gene therapy. Here, we have tried to give comprehensive coverage to some major cases of antisense RNA control of cancer-related genes highlighting the biological systems involved, the efficacy of the antisense RNA in altering target gene function, and how such antisense control affects the malignant phenotype. Furthermore, the therapeutic potential of the antisense technique depends on the in-depth understanding of the target gene function and its role in carcinogenesis.
Mukhopadhyay
T
T
Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Roth
J A
JA
D000818:Animals; D002273:Carcinogens; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D012313:RNA / Q000235:genetics; D016337:RNA, Catalytic / Q000235:genetics
D002273:Carcinogens; D016376:Oligonucleotides, Antisense; D016337:RNA, Catalytic; D012313:RNA