Antisense approaches in prostate cancer.
Patients with hormone refractory prostate cancer have limited treatment options and new therapies are urgently needed. Advances in the understanding of the molecular mechanisms implicated in prostate cancer progression have identified many potential therapeutic gene targets that are involved in apoptosis, growth factors, cell signalling and the androgen receptor (AR). Antisense oligonucleotides are short sequences of synthetic modified DNA that are designed to be complimentary to a selected gene's mRNA and thereby specifically inhibit expression of that gene. The antisense approach continues to hold promise as a therapeutic modality to target genes involved in cancer progression, especially those in which the gene products are not amenable to small molecule inhibition or antibodies. The current status and future direction of a number of antisense oligonucleotides targeting several genes, including BCL-2, BCL-XL, clusterin, the inhibitors of apoptosis (IAP) family, MDM2, protein kinase C-alpha, c-raf, insulin-like growth factor binding proteins and the AR, that have potential clinical use in prostate cancer are reviewed.
Chi
Kim N
KN
BC Cancer Agency, 600 West 10th Avenue, Vancouver, British Columbia, V5Z 4E6, Canada. kchi@bccancer.bc.ca
Gleave
Martin E
ME
D017209:Apoptosis; D051152:Clusterin; D018450:Disease Progression; D006023:Glycoproteins / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism; D008297:Male; D008957:Models, Genetic; D018832:Molecular Chaperones / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000628:therapy*; D011493:Protein Kinase C / Q000378:metabolism; D051571:Protein Kinase C-alpha; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D011944:Receptors, Androgen / Q000378:metabolism; D015398:Signal Transduction
C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D006133:Growth Substances; D018971:Insulin-Like Growth Factor Binding Protein 2; D018975:Insulin-Like Growth Factor Binding Protein 5; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011944:Receptors, Androgen; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha