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Die nächste Stufe der sequentiellen Androgenblockade ….

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    Die nächste Stufe der sequentiellen Androgenblockade ….

    Dutasteride and enzalutamide synergistically suppress prostate tumor cell proliferation
    The Journal of Urology, 10/30/2014 Clinical Article



    Hamid ARAH, et al. – In this study, authors hypothesize that a combination of a SRD5A inhibitor and an antiandrogen, would both block intratumoral androgen synthesis as well as AR protein activity, and hence would act synergistically in reducing tumor cell proliferation. They found that combination of a SRD5A inhibitor and (novel) antiandrogens, synergistically inhibited tumor cell proliferation. These findings support clinical studies with combinations of a SRD5A inhibitor and (novel) antiandrogens for the first line treatment of PCa and CRPC.
    Methods
    • The expression level of SRD5A and AR in endocrine therapy naive PCa and CRPC tissue and cell line models were determined using microarray and qPCR analysis.
    • Intracellular androgen levels were measured with radioimmunoassay.
    • Tumor cell proliferation were determined using coloric MTT assays.
    • Synergistic effects of combination treatments on tumor cell proliferation were calculated using the Chou Talalay equation.

    Results
    • SRD5A1 and SRD5A3 were upregulated in all PCa cases, and the AR was upregulated in metastatic PCa and in CRPC.
    • Dutasteride, a SRD5A inhibitor, effectively reduced DHT production in PCa and CRPC cell lines.
    • Furthermore, dutasteride in combination with the novel antiandrogen, enzalutamide, synergistically suppressed endocrine therapy naive PCa and CRPC cell proliferation.

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