Antisense cancer therapy: the state of the science.
Over the last few years, antisense technology has emerged as an exciting and promising strategy in the fight against cancer. The antisense concept is to selectively bind short, modified DNA or RNA molecules to messenger RNA in cells and prevent the synthesis of the encoded protein. As anticancer agents, these molecules can be targeted against a myriad of genes involved in cell transformation, cell survival, metastasis, and angiogenesis. Indeed, the list of possible antisense targets increases as the knowledge of the genetic basis of oncogenesis expands. One aim of this review is to focus on those antisense cancer drugs that have entered human clinical trials. At least four of these compounds are currently in phase II trials, including those targeting protein kinase C-alpha, bcl-2, c-raf, and the R1-alpha subunit of protein kinase A. A new development in antisense chemistry (peptide nucleic acids) is discussed, along with alternative antisense-related strategies (ribozymes and 2-5A-antisense) designed to overcome some of the challenges of this already encouraging technology.
Kushner
D M
DM
Department of Gynecology and Obstetrics, The Cleveland Clinic Foundation, Cleveeland OH 44195, USA.
Silverman
R H
RH
D002986:Clinical Trials as Topic; D016313:Genes, abl / Q000235:genetics; D019254:Genes, bcl-2 / Q000235:genetics; D020570:Genes, myb / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy*; D020320:Oligoribonucleotides, Antisense / Q000627:therapeutic use*; D020135:Peptide Nucleic Acids / Q000627:therapeutic use; D011493:Protein Kinase C / Q000235:genetics*; D051571:Protein Kinase C-alpha; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics; D016337:RNA, Catalytic
D007527:Isoenzymes; D020320:Oligoribonucleotides, Antisense; D020135:Peptide Nucleic Acids; D016337:RNA, Catalytic; D019908:Proto-Oncogene Proteins c-raf; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha