Antisense therapy: current status in prostate cancer and other malignancies.
Recent technological advances now allowing both large scale data generation and its in-depth analysis have opened new avenues to identify and target genes involved in neoplastic transformation and tumor progression. This accelerated identification and characterization of cancer-relevant molecular targets has sparked considerable interest in the development of new generations of anti-cancer agents. It is anticipated, that these agents will show enhanced specificity for malignant cells and a more favorable side-effect profile due to well-defined and tailored modes of action. Antisense oligonucleotides (ASOs) are short synthetic stretches of chemically modified DNA capable of specifically hybridizing to the mRNA of a chosen cancer-relevant target gene are close, after decades of challenges, close to fulfilling their promise in the clinical setting. Emerging clinical evidence supports the notion that ASOs stand a realistic chance of developing into one of the main players of rationally designed anti-cancer agents, although certainly not all of the challenges have been met to date. The status of antisense targeting of genes relevant to prostate cancer, including bcl-2, bcl-xL, clusterin, androgen receptor (AR) and IGFBPs, are reviewed.
Gleave
Martin
M
The Prostate Centre, Vancouver General Hospital, Division of Urology, University of British Columbia, Canada. gleave@interchange.ubc.ca
Miyake
Hideake
H
Zangemeister-Wittke
Uwe
U
Jansen
Burkhard
B
D059002:Androgen Receptor Antagonists; D017209:Apoptosis / Q000235:genetics; D051152:Clusterin; D019254:Genes, bcl-2 / Q000235:genetics; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D008297:Male; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000628:therapy*; D011944:Receptors, Androgen / Q000235:genetics
D059002:Androgen Receptor Antagonists; C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones; D016376:Oligonucleotides, Antisense; D011944:Receptors, Androgen