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Updated: Jul 3, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
[Feasibility of targeted therapy based on immunohistochemical expression analysis in androgen-independent prostate
C-H Ohlmann1, E Markert, M Gerharz
1Klinik für Urologie und Kinderurologie, Universitätsklinikum des Saarlandes, Homburg/Saar, Deutschland. Carsten.Ohlmann@uks.eu
Abstract:
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 (PDGFRbeta), 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%, PDGFRbeta 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 > or =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.
Insights
Targeted therapies show promise for advanced prostate cancer. Most patients with androgen-independent prostate cancer (AIPC) express molecular markers, enabling personalized treatment strategies with signal transduction inhibitors and docetaxel.
Area of Science:
- Oncology
- Molecular Biology
Background:
- Targeted therapies offer novel treatment avenues for prostate cancer.
- Androgen-independent prostate cancer (AIPC) presents a significant clinical challenge.
- Identifying molecular targets is crucial for effective AIPC treatment.
Purpose of the Study:
- To analyze the expression profile of molecular markers in AIPC patients.
- To evaluate the efficacy of combination therapy with signal transduction inhibitors (STIs) and docetaxel based on expression profiles.
Main Methods:
- Immunohistochemical analysis of tumor tissue for EGFR, PDGFRbeta, Her-2/neu, c-KIT, and VEGF.
- Treatment of patients with corresponding STIs and docetaxel based on marker expression.
- Evaluation of treatment response by prostate-specific antigen (PSA) decline and survival time.
Main Results:
- 90.2% of 51 AIPC patients expressed one or more target markers.
- EGFR (61.2%), PDGFRbeta (57.1%), and VEGF (74.5%) were highly expressed.
- In a small cohort (n=8), 50% achieved a >=50% PSA decline with combination therapy, median survival 13.5 months.
Conclusions:
- Molecular targets are prevalent in AIPC, supporting personalized treatment approaches.
- Combination therapy with STIs and docetaxel shows potential clinical benefit.
- Further clinical studies are warranted to confirm the efficacy of molecular targeted therapy in AIPC.
