Toward antisense oligonucleotide therapy for cancer: ISIS compounds in clinical development.
Antisense oligonucleotides offer the promise of therapeutic effect with few toxic effects, by virtue of their high selectivity. Preclinical studies have provided evidence of antisense effects in vitro and in vivo, and phase I clinical trials have demonstrated safety, feasibility and activity of antisense oligonucleotides for the treatment of cancer. This review summarizes the status of development of three anticancer antisense oligonucleotides from ISIS Pharmaceuticals.
Holmlund
J T
JT
ISIS Pharmaceuticals Inc, Carlsbad, CA 92008, USA. jholmlun@ISISph.com
Monia
B P
BP
Kwoh
T J
TJ
Dorr
F A
FA
D000818:Animals; D001778:Blood Coagulation Disorders / Q000139:chemically induced; D017321:Clinical Trials, Phase I as Topic; D003170:Complement Pathway, Alternative / Q000187:drug effects; D004334:Drug Administration Schedule; D015195:Drug Design; D004347:Drug Interactions; D005221:Fatigue / Q000139:chemically induced; D005240:Feasibility Studies; D005260:Female; D005334:Fever / Q000139:chemically induced; D005544:Forecasting; D011905:Genes, ras; D015316:Genetic Therapy; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D020319:Oligodeoxyribonucleotides, Antisense / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D016376:Oligonucleotides, Antisense / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D010314:Partial Thromboplastin Time; D054735:Phosphorothioate Oligonucleotides; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics; D051571:Protein Kinase C-alpha; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000037:antagonists & inhibitors; D012449:Safety; D013873:Thionucleotides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
C122000:ISIS 2503; D007527:Isoenzymes; D009363:Neoplasm Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D016376:Oligonucleotides, Antisense; D054735:Phosphorothioate Oligonucleotides; D013873:Thionucleotides; C108494:ISIS 3521; C099587:ISIS 5132; D019908:Proto-Oncogene Proteins c-raf; C496628:PRKCA protein, human; C496630:Prkca protein, mouse; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); C089753:alicaforsen; C091346:fomivirsen