Knock-down of the cytoprotective gene, clusterin, to enhance hormone and chemosensitivity in prostate and other cancers.
Discovery and targeting of genes mediating treatment resistance may lead to development of novel therapies that delay progression of recurrent and refractory cancers. Clusterin is a stress-associated cytoprotective chaperone expressed in many cancers that is upregulated in an adaptive cell survival manner by various apoptotic triggers and confers treatment resistance. Here, we review clusterin's functional role in regulating treatment-induced apoptosis and the use of a second generation antisense oligonucleotide to inhibit clusterin expression to enhance the cytotoxic effects of hormone- and chemotherapy in prostate and other xenograft models, as well as in recent human trials.
Gleave
Martin
M
Division of Urology, University of British Columbia, The Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia V5Z 3J5, Canada. gleave@interchange.ubc.ca
Chi
Kim N
KN
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002986:Clinical Trials as Topic; D051152:Clusterin / Q000235:genetics* / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D000970:Antineoplastic Agents; D051152:Clusterin; D006728:Hormones; D019253:Proto-Oncogene Proteins c-bcl-2