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 Printable version |
Molecular mechanisms involved in hormone resistance of prostate cancer |
Bulletin du Cancer. Volume 91, Number 10, 747-57, Octobre 2004, Synthèse
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 Résumé
Article gratuit
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Author(s) : Aurélie Cabrespine , Laurent Guy , Philippe Chollet , Éric Debiton , Jacques-Olivier Bay |
Summary : Prostate cancer has an androgen-dependant growth mediated by the androgen receptor (AR). Androgen pathway blockage is the standard therapy for the treatment of prostate cancers at an advanced stage. In spite of an initial sensitivity, prostate cancers become more or less quickly towards androgen-independant. Hormone refractory can be due to amplification of AR gene, AR mutations and the increase in co-activator protein expression or in the 5α-reductase activity. These induce an agonist activity with the anti-androgens or others steroid hormones like estrogens on AR and allow AR activation with weak concentrations of androgens. Growth factors and cytokines can induce AR phosphorylation independently of the ligand fixation. In condition of androgenic deprivation, AR remains actively involved in the growth of the cancerous cells prostate. Nevertheless, there are others partial AR-independent pathways as neuroendocrine differentiation. The comprehension of these various mechanisms is the key of the development of more effective therapies on hormono-refractory prostate cancers. |
Keywords : prostate cancer, hormone-refractory, androgen receptor, growth factors, cytokines |
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