Signal transduction as target of gene therapy.
Cancer development involves multistep events. Therapeutic approaches can be targeted against any of these events individually or in combination. Pancreatic cancer can involve activation of Ki-Ras, overexpression of Myc or ErbB-2, and mutational inactivation of functional p53. Three approaches with nucleic acid-based therapies have been taken. A ribozyme specific for Ki-ras mRNA carrying the activating mutation in codon 12 (GGU to GUU) was designed and shown to be stimulated by interaction with an RNA-binding protein NCp7 of HIV-1. The same protein was targeted to cell-adhesion molecules, which allowed transfer of the ribozyme and an antisense oligodeoxynucleotide (ODN) into the cell. Furthermore, proliferation may be prevented by blocking signal transduction. A transdominant negative mutant of the signaling kinase c-Raf-1 efficiently blocked transmission. A retroviral vector will be used as carrier. Furthermore, the concept of using naked DNA injected intramuscularly as an immunogen against cancer is discussed.
Moelling
K
K
Institute of Medical Virology, University of Zürich, Switzerland.
Strack
B
B
Radziwill
G
G
D000595:Amino Acid Sequence; D011905:Genes, ras; D015316:Genetic Therapy; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000628:therapy*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019908:Proto-Oncogene Proteins c-raf; D016337:RNA, Catalytic / Q000494:pharmacology; D015398:Signal Transduction
D011518:Proto-Oncogene Proteins; D016337:RNA, Catalytic; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf