title: Preclinical and clinical experience of antisense therapy for solid tumors.
abstract: The mechanisms by which the therapeutic window and clinical utility of antisense drugs can be fully optimized are discussed. Recent preclinical and clinical efforts are focusing on defining and optimizing the combination therapy regimes in which ONs are most efficacious. However, additional research is required to define which, and how, oncogenes interact with each other and the circumstances under which synergistic therapeutic benefit might be achieved using antisense drugs. The therapeutic window of antisense drugs is also being expanded by the use of novel delivery systems, including lipid-based carriers for systemic delivery. Taken together, molecular therapeutics based on antisense technology, coupled with effective delivery systems increasing drug potency, are anticipated to substantially improve the treatment of human neoplasms.
authors.affiliation: Inex Pharmaceuticals Corporation, Bumaby, BC, Canada. mwebb@inexpharm.com
authors.forename: M S
authors.initials: MS
authors.lastname: Webb
authors.forename: G
authors.initials: G
authors.lastname: Zon
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001682:Biological Availability; D002463:Cell Membrane Permeability; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003131:Combined Modality Therapy; D004333:Drug Administration Routes; D015195:Drug Design; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000008:administration & dosage; D008297:Male; D051379:Mice; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D008055:Lipids; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D015513:Oncogene Proteins; D014677:Pharmaceutical Vehicles