Antisense oligonucleotides for cancer therapy-an overview.
Antisense technology has emerged as an exciting and promising strategy of cancer therapy. The principle of this technology is the sequence-specific binding of an antisense oligonucleotide to target mRNA, resulting in the prevention of gene translation. The specificity of hybridization by Watson-Crick base pairing make antisense oligonucleotides attractive as tools for targeted validation and functionalization, and as therapeutics to selectively modulate the expression of genes involved in the pathogenesis of malignancies and other genetic diseases. A variety of genes known to be key regulators of apoptosis, cell growth, metastasis, and angiogenesis which are associated with the malignant phenotype of cancer cells rather than with normal cell physiology, have been validated as molecular targets for antisense therapy. One antisense compound has been approved for local treatment of cytomegalovirus-induced retinitis, and several others are in clinical trials, including those targeting the mRNA of Bcl-2, protein kinase C-alpha (PKC-alpha), c-raf or Ha-ras. In this review, we focus on the mechanism of action of antisense oligonucleotides and new technical developments, look at new targets provided by coordinated functional genomics and proteomics initiatives and summarize the most promising clinical data.
Stahel
Rolf A
RA
Division of Medical Oncology, University Hospital, Rämistrasse 100, Zurich 8091, Switzerland. rolf.stahel@usz.ch
Zangemeister-Wittke
Uwe
U
D002986:Clinical Trials as Topic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger