Clinical studies of antisense therapy in cancer.
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.
Yuen
A R
AR
Oncology Division, 703 Welch Road, Suite H4, Palo Alto, CA 94304, USA. ayuen@stanford.edu
Sikic
B I
BI
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D016376:Oligonucleotides, Antisense