Clusterin and IGFBPs as antisense targets in prostate cancer.
The primary hurdle to improved survival of advanced prostate cancer is our failure to prevent or treat the tumor's progression to its lethal and untreatable stage of androgen independence. Novel treatment modalities designed to prevent androgen-independent progression including prostate cancer metastasis are required. Accelerated identification and characterization of cancer-relevant molecular targets has sparked considerable interest in the development of new generations of anticancer agents that specifically inhibit a progression-relevant target. Antisense oligonucleotides, short synthetic stretches of chemically modified DNA capable of specifically hybridizing to the mRNA of a chosen cancer-relevant target gene, promise to show enhanced specificity for malignant cells with a favorable side-effect profile due to well-defined and tailored modes of action. Although not all of the challenges have been met to date, emerging clinical evidence supports the premise that antisense oligonucleotides stand a realistic chance of emerging as major partners of rationally designed anticancer regimens. The rationale and status of antisense targeting of the treatment resistance factor clusterin and of insulin-like growth factor binding protein (IGFBP) 2 and 5 are discussed.
Gleave
Martin
M
The Prostate Centre at Vancouver General Hospital, Division of Urology, University of British Columbia, Vancouver, BC, Canada, V6H 3Z3. gleave@interchange.ubc.ca
Jansen
Burkhard
B
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D051152:Clusterin; D006023:Glycoproteins / Q000187:drug effects*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000187:drug effects*; D008297:Male; D018832:Molecular Chaperones / Q000187:drug effects*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D018969:Insulin-Like Growth Factor Binding Proteins; D018832:Molecular Chaperones; D016376:Oligonucleotides, Antisense