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Prostate cancer

Androgen receptor (AR); clusterin (CLU; APOJ)

Cell 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 compound OGX-011 (TV-1011) and the anti-AR drug Xtandi enzalutamide 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.
Medivation 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.

SciBX 6(30); doi:10.1038/scibx.2013.791
Published online Aug. 8, 2013

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Matsumoto, H. et al. Cancer Res.; published online June 20, 2013;
Contact: Martin Gleave, The University of British Columbia, Vancouver, British Columbia, Canada