Objectives: In order to improve the efficacy of targeted therapy trials, the expression profiles of several molecular markers that are potential candidates for targeted therapy were analyzed in patients with progressive castration-resistant prostate cancer.Methods and materials: Paraffin-embedded samples of tumor tissue from 51 patients obtained from biopsies of metastases or remaining prostates were analyzed immunohistochemically for the expression of EGFR, PDGFR beta, Her-2/neu, c-Kit, and VEGF. Staining was analyzed according to the percentage of positively stained tumor cells and the intensity of staining.Results: According to the different cut-off values of 10%, 30%, 50%, or 70% for the percentage of positively stained cells, different rates of expression were found. Expression rates ranged from 30.6% to 61.2% for EGFR, from 34.7% to 57.1% for PDGFR beta, from 9.6% to 28.8% for Her-2/neu, from 12.5% to 22.4% for c-Kit, and from 51.1% to 74.5% for VEGF. Defining positive expression as >= 30% positively stained tumor cells, with an intensity of staining of >= 2+, resulted in positive expression of EGFR in 38.8%, PDGFR beta in 24.5%, Her-2/neu in 13.5%, c-Kit in 6.4%, and VEGF in 44.7% of the patients.Conclusions: Our results demonstrate simultaneous expression of several markers in castration-resistant prostate cancer tissue. Translation of the results into modern, multi-arm clinical trial designs will improve the efficacy of recruiting and obtaining results, compared with multiple double-arm trials. (C) 2011 Elsevier Inc. All rights reserved.

Molekular getriggerte Therapien, sog. „targeted therapies“ haben bereits bei einigen Tumorentitäten die konventionelle Chemotherapie ersetzt und stellen auch für das Prostatakarzinom eine interessante Therapieoption dar. Ziel unserer Studie war es, potentiell therapeutisch nutzbare molekulare Marker für eine „targeted therapy“ beim hormonrefraktären Prostatakarzinom zu analysieren und anhand des Markerprofils eine individualisierte Therapie mit einem Antikörper bzw. einem Tyrosinkinaseinhibitor einzuleiten.

Targeted therapies present an interesting treatment option in prostate cancer. The aim of our study was to analyze the expression profile of several molecular markers that are candidates for targeted therapy in patients with progressive androgen-independent prostate cancer (AIPC). Based on the expression profile, the efficacy of a combination therapy with a signal transduction inhibitor (STI) and docetaxel was evaluated. Tumor tissue obtained from biopsy of the prostate or lymph node and visceral metastasis was analyzed for the immunohistochemical expression of epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor beta (PDGFR beta), Her-2/neu, c-KIT, and vascular endothelial growth factor (VEGF). Patients with positive staining of one or more markers were treated with the corresponding STI and docetaxel. Fifty-one patients were included in the protocol, of whom 43 (84.3%) presented with progressive AIPC after first-line chemotherapy. Forty-six of these 51 patients (90.2%) showed expression of one or more of the analyzed markers. Expression of EGFR was found in 61.2%, PDGFR beta in 57.1%, Her-2/neu in 16.3%, c-KIT in 25.0%, and VEGF in 74.5%. After request for cost coverage, 8/51 patients received the combination therapy and were evaluated for response. Four of the eight patients (50%) showed a decline in prostate-specific antigen of >= 50%, and median survival time was 13.5 months at a median follow-up of 23.6 (11-35) months. The results show that expression of molecular targets is found in about 90% of patients with AIPC. Based on the expression profile, an individual treatment strategy can be applied to each patient. Further clinical studies should determine the clinical efficacy of molecular targeted therapy in patients with AIPC.