Antisense oligonucleotide inhibition of serine/threonine kinases: an innovative approach to cancer treatment.
The identification of genes that confer a growth advantage on neoplastic cells and the understanding of the genetic mechanism(s) responsible for their activation have made possible a direct genetic approach to cancer treatment using nucleic acid therapeutics. Moreover, the ability to block the expression of individual genes that promote carcinogenesis provides a powerful tool to explore the molecular basis of normal growth regulation, as well as the opportunity for therapeutic intervention. One technique for turning off a single activated gene is the use of antisense oligodeoxynucleotides and their analogs for inhibition of gene expression. The serine/threonine kinases are involved in mediating intracellular responses to external signals, such as growth factors, hormones, and neurotransmitters, and are involved in cell proliferation and oncogenesis. Described herein are recent studies supporting the potential use of oligonucleotides targeting these kinases as chemotherapeutic agents for cancer treatment. The serine/threonine kinases included here are protein kinase A, protein kinase C, and c-raf-1 kinase.
Cho-Chung
Y S
YS
Cellular Biochemistry Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1750, USA.
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016376:Oligonucleotides, Antisense; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C