Bicalutamide Demonstrates Biologic Effectiveness in Prostate Cancer Cell Lines and Tumor Primary Cultures Irrespective of Her2/neu Expression Levels

OBJECTIVES To evaluate the role of Her2/neu as a molecular marker predictive of the treatment response to bicalutamide in prostate cancer (PCa). METHODS Four PCa cell lines with graded Her2/neu expression levels and 63 primary tumor cultures derived from men with PCa and selected according to Her2/neu tumor levels were used. Primary tumor Cultures and PCa cell lines were treated with bicalutamide (0.1-10 mu M) in the presence of dehydrotestosterone (10(-12) M) for 4 days. The presence of a significant correlation between Her2/nue expression and drug efficacy was used to define the role of Her2/neu as molecular predictor of bicalutamide effectiveness. As an indicator of drug effectiveness we used the concentration that inhibits 50% values determined after bicalutamide treatment. RESULTS After bicalutamide treatment, no significant differences in the concentration that inhibits 50% were found among the different tumor cell lines (P =.081). In this experimental model, the correlation analysis suggested that the effectiveness of this drug was not influenced by Her2/neu levels (r = 0,053, P =.823). In primary Cultures with high Her2/neu levels (43 tumor Cultures), the mean value of the concentration that inhibits 50% for bicalutamide was 0.43 +/- 0.13 mu M, and in cultures with low, Her2/neu levels (20 tumor cultures), the same parameter was 0.5 +/- 0.16 mu M (P =.14). The correlation analysis Suggested that the effectiveness of this drug was not influenced by Her2/neu levels (r = 0.33, P =.101). CONCLUSIONS Our biologic data seem to indicate that the antitumor effect of bicalutamide is independent of Her2/neu levels in preclinical models of PCa. Bicalutamide Could be configured as a pharmacologic option to treat patients with high or tow levels of Her2/neu. UROLOGY 74: 452-457, 2009. (C) 2009 Elsevier Inc.