Thursday, August 8, 2013
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Androgen receptor (AR); clusterin (CLU; APOJ)
culture and mouse studies suggest dual inhibition of AR and CLU can delay
progression of castration-resistant prostate cancer (CRPC). Overexpression of
CLU is known to confer resistance to AR inhibitors. In AR-responsive human
prostate cancer cell lines, combined treatment with the CLU antisense
and the anti-AR drug Xtandi
synergistically decreased growth and increased apoptosis compared with either
treatment alone. In castrated male mice with human prostate cancer cells, the
combination showed greater antitumor effects and increased survival compared
with enzalutamide alone. Next steps could include combinatorial clinical
studies with inhibitors of AR and CLU.
Inc. markets enzalutamide to treat CRPC.
At least four other companies market AR antagonists to treat cancer.
OGX-011 from OncoGenex
Pharmaceuticals Inc., Isis
Pharmaceuticals Inc. and Teva
Pharmaceutical Industries Ltd. is in Phase III testing to
treat non-small cell lung cancer (NSCLC) and prostate cancer.
At least two other companies have CLU inhibitors in preclinical development
to treat cancer.
Published online Aug. 8, 2013
Patent and licensing status
Matsumoto, H. et al.
Cancer Res.; published online June 20, 2013;
Contact: Martin Gleave, The University of British Columbia, Vancouver,
British Columbia, Canada
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