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Updated: May 5, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Immunohistochemical expression of PDGFR, VEGF-C, and proteins of the mToR pathway before and after androgen
Nicolas Kozakowski1, Caroline Hartmann, Hans Christoph Klingler
1Clinical Institute for Pathology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Abstract:
Targeted therapy in hormone refractory prostate cancer (HRPC) is currently under evaluation in many trials. The effect of androgen deprivation therapy (ADT) on many targets in prostate cancer is incompletely known. For the first time, immunohistochemical expression of the platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR), vascular endothelial growth factor C (VEGF-C), mammalian target of rapamycin (mToR), p70 ribosomal protein S6 kinase 1 (PS6K), human epidermal growth factor receptor 2 (c-erbB-2), and carbonic anhydrase IX (CA9) was evaluated in 44 patients with prostate carcinoma treated with or without ADT, at biopsy time and after radical prostatectomy. PDGFR, VEGF-C, mToR, and PS6K expression was significantly reduced (p = 0.002, p = 0.035, p = 0.025, and p = 0.033, respectively) after ADT, whereas expression of EGFR, c-erbB-2, and CA9 was not influenced by ADT. In conclusion, targeting PDGFR, VEGF-C, mToR, or PS6K after ADT should be considered with precaution, as those targets can severely be altered or functionally deregulated by ADT.
Insights
Androgen deprivation therapy (ADT) significantly reduces key targets like PDGFR, VEGF-C, mTOR, and PS6K in prostate cancer. Caution is advised when targeting these pathways post-ADT due to potential alterations.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Hormone-refractory prostate cancer (HRPC) targeted therapies are under investigation.
- The impact of androgen deprivation therapy (ADT) on prostate cancer molecular targets is not fully understood.
Purpose of the Study:
- To evaluate the expression of key growth factor receptors and signaling molecules in prostate cancer patients treated with or without ADT.
- To determine how ADT affects the expression of PDGFR, EGFR, VEGF-C, mTOR, PS6K, c-erbB-2, and CA9.
Main Methods:
- Immunohistochemical analysis of 7 molecular targets in 44 prostate carcinoma patients.
- Samples were assessed at biopsy and post-radical prostatectomy, comparing patients with and without ADT.
Main Results:
- ADT significantly reduced the expression of platelet-derived growth factor receptor (PDGFR), vascular endothelial growth factor C (VEGF-C), mammalian target of rapamycin (mTOR), and p70 ribosomal protein S6 kinase 1 (PS6K).
- Expression of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (c-erbB-2), and carbonic anhydrase IX (CA9) remained unaffected by ADT.
Conclusions:
- Targeting PDGFR, VEGF-C, mTOR, or PS6K in prostate cancer patients undergoing ADT requires careful consideration.
- ADT can significantly alter or functionally deregulate these targeted pathways, impacting treatment efficacy.
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