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.
MeSH terms
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Adenocarcinoma / drug therapy
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Adenocarcinoma / secondary*
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Adenocarcinoma / surgery
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Androgen Antagonists / therapeutic use
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Androgens / metabolism
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Antineoplastic Agents, Hormonal / pharmacology
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Antineoplastic Agents, Hormonal / therapeutic use*
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Antineoplastic Combined Chemotherapy Protocols / pharmacology
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Apoptosis
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Bone Neoplasms / drug therapy
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Bone Neoplasms / metabolism
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Bone Neoplasms / secondary*
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Clinical Trials, Phase II as Topic
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Combined Modality Therapy
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Dexamethasone / administration & dosage
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Dexamethasone / pharmacology
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Drug Resistance, Neoplasm
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Estramustine / administration & dosage
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Etoposide / administration & dosage
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Gonadotropin-Releasing Hormone / analogs & derivatives
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Gonadotropin-Releasing Hormone / therapeutic use
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Growth Substances / metabolism
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Humans
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Leuprolide / administration & dosage
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Male
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Neoplasm Proteins / metabolism
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Neoplasms, Hormone-Dependent / drug therapy
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Neoplasms, Hormone-Dependent / metabolism
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Neoplasms, Hormone-Dependent / secondary
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Neoplasms, Hormone-Dependent / surgery
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Orchiectomy
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Osteoblasts / metabolism
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Osteoclasts / metabolism
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Paracrine Communication
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Peptides, Cyclic / administration & dosage
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Prospective Studies
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Prostatic Neoplasms / drug therapy*
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Prostatic Neoplasms / surgery
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Randomized Controlled Trials as Topic
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Receptors, Androgen / drug effects
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Receptors, Androgen / metabolism
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Salvage Therapy
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Somatostatin / administration & dosage
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Somatostatin / analogs & derivatives
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Survival Analysis
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Triptorelin Pamoate / administration & dosage
Substances
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Androgen Antagonists
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Androgens
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Antineoplastic Agents, Hormonal
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Growth Substances
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Neoplasm Proteins
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Peptides, Cyclic
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Receptors, Androgen
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Triptorelin Pamoate
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lanreotide
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Gonadotropin-Releasing Hormone
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Estramustine
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Somatostatin
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Etoposide
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Dexamethasone
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Leuprolide