Abstract

The ability to target and inhibit individual gene expression with antisense oligonucleotides has shown promising activity in preclinical cancer models. Recent clinical studies have tested antisense compounds directed against seven cancer related genes including p53, bcl-2, c-raf, H-ras, protein kinase C-alpha, and protein kinase A. Class specific effects of the phosphorothioate backbone common to the first generation of antisense compounds have dominated the side effects of these oligonucleotides. Inhibition of target gene expression has been modest at most, and clinical activity has been primarily anecdotal. Combinations of the antisense compounds with chemotherapy and second-generation oligonucleotides offer promise that these agents might become a standard part of future cancer therapy.

View details for Web of Science ID 000089664000003

View details for PubMedID 10833467