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Updated: Aug 7, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Combination therapy using LHRH and somatostatin analogues plus dexamethasone in androgen ablation refractory prostate
Michael Koutsilieris1, John Bogdanos, Constantine Milathianakis
1University of Athens, Department of Basic Sciences, Medical School, 75 Micras Asias, Goudi-Athens 11527, Greece. mkouts@medscape.com
Abstract:
The development of resistance to anticancer therapies is a major hurdle in preventing long-lasting clinical responses to conventional therapies in hormone-refractory prostate cancer. Herein, the molecular evidence documenting that bone metastasis microenvironment survival factors (mainly the paracrine growth hormone-independent, urokinase-type plasminogen activator-mediated increase of IGF-1 and the endocrine production of growth hormone-dependent IGF-1, mainly liver-derived IGF-1 production) produce an epigenetic form of prostate cancer cells that are resistant to proapoptotic therapies is reviewed. Consequently, the authors present the conceptual framework of a novel antibone microenvironment survival factor, mainly an anti-IGF-1 hormonal manipulation for androgen ablation refractory prostate cancer (a combination of conventional androgen ablation therapy [luteinising hormone-releasing hormone agonist-A or orchiectomy]) with dexamethasone plus somatostatin analogue, which yielded durable objective responses and major improvement of bone pain and performance status in stage D3 prostate cancer patients.
Insights
Prostate cancer resistance to therapy is linked to bone microenvironment factors promoting survival. A novel anti-IGF-1 therapy combining androgen deprivation with dexamethasone and somatostatin analogue shows promise.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Therapy resistance is a significant challenge in advanced prostate cancer.
- Bone metastasis microenvironment survival factors contribute to treatment resistance.
- Insulin-like Growth Factor 1 (IGF-1) plays a critical role in prostate cancer cell survival and therapy resistance.
Purpose of the Study:
- To review the molecular mechanisms of therapy resistance in prostate cancer.
- To present a novel therapeutic strategy targeting the bone microenvironment in hormone-refractory prostate cancer.
Main Methods:
- Review of molecular evidence on bone metastasis microenvironment survival factors.
- Conceptual framework for a novel anti-IGF-1 hormonal manipulation strategy.
- Clinical evaluation of the novel combination therapy in stage D3 prostate cancer patients.
Main Results:
- Bone metastasis microenvironment survival factors, particularly IGF-1, promote epigenetic resistance to proapoptotic therapies.
- The novel anti-IGF-1 hormonal manipulation (androgen ablation therapy, dexamethasone, somatostatin analogue) demonstrated durable objective responses.
- Significant improvements in bone pain and performance status were observed in treated patients.
Conclusions:
- Targeting bone microenvironment survival factors, specifically IGF-1, is a viable strategy for hormone-refractory prostate cancer.
- Combination hormonal therapy offers a promising approach for managing advanced prostate cancer with bone metastases.
- This strategy may overcome resistance mechanisms and improve patient outcomes.
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