El Hassane Sidibé

Prostate Proto-Oncogene Molecular Action El Hassane Sidibé

MEK inhibition alone was less effective in inducing cytotoxicity than taxanes indicating that a down-regulation of activated ERK1/2 may be necessary but is not sufficient for taxane-induced antitumoral effects. In line with this notion, we show in a xenograft mouse model that prostate cancer cells that are resistant to docetaxel overexpress activated ERK1/2. Taken together, our findings underscore that the modulation of ERK1/2 activation, in concert with other mechanisms, plays an important role in taxane-induced antineoplastic effects on prostate cancer cells. These results suggest at least partially nonoverlapping effects of docetaxel and androgen deprivation therapy and hence help to understand recent clinical findings. A further elucidation of the mode of action of docetaxel would have important implications to optimize current treatment strategies and biomarker development for men with metastatic prostate cancer.