Antisense strategies targeting protein kinase C: preclinical and clinical development.

Abstract

Altered protein kinase C-alpha (PKC-alpha) expression has been implicated in tumor promotion and carcinogenesis. One potentially attractive therapeutic intervention may be the use of selective antisense oligonucleotides to inhibit production of PKC-alpha. In preclinical studies, the antisense oligonucleotide LY900003 (ISIS 3521;Affinitak; Isis Pharmaceuticals, Carlsbad, CA) has shown selective inhibition of PKC-alpha mRNA and protein expression and has shown antitumor activity. In clinical studies, LY900003 has shown activity as a single agent, but the most promising data have been obtained in combination with chemotherapy, particularly in patients with non-small cell lung cancer. Data from phase I and II studies have led to ongoing randomized phase III trials in combination with either cisplatin and gemcitabine or carboplatin and paclitaxel. Studies in other tumor types will also investigate the benefit of combining LY900003 with conventional chemotherapy.

• Authors: Giampaolo Tortora, Fortunato Ciardiello
• Journal: Seminars in oncology (Semin Oncol) Vol. 30 Issue 4 Suppl 10 Pg. 26-31 (Aug 2003) ISSN: 0093-7754 [Print] United States
• PMID: 12917818 (Publication Type: Journal Article, Review)

Chemical References

• Oligodeoxyribonucleotides, Antisense
• Oligonucleotides, Antisense
• Thionucleotides
• ISIS 3521
• Protein Kinase C

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (therapy)
• Humans
• Lung Neoplasms (therapy)
• Oligodeoxyribonucleotides, Antisense (administration & dosage, therapeutic use)
• Oligonucleotides, Antisense (administration & dosage, therapeutic use)
• Protein Kinase C (antagonists & inhibitors, genetics)
• Randomized Controlled Trials as Topic
• Thionucleotides (administration & dosage, therapeutic use)