Molecular alterations and emerging targets in castration resistant prostate cancer |
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| Affiliation: | 1. Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA;2. Division of Clinical Pharmacology, Stellenbosch University, Cape Town, South Africa;3. Children''s Infectious Diseases Clinical Research Unit, Tygerberg Children''s Hospital and Stellenbosch University, Cape Town, South Africa;1. Hospices Civils de Lyon, Centre Hospitalier Lyon Sud Pierre Bénite, Department of Oncologic and General Surgery, France;2. UMR 37-38, Université Lyon 1, Lyon, France;3. Hospices Civils de Lyon, Centre Hospitalier Lyon Sud Pierre Bénite, Gynecology Department, France;4. Hospices Civils de Lyon, Centre Hospitalier Lyon Sud Pierre Bénite, Department of Biology, France;5. Hospices Civils de Lyon, Pole IMER, Lyon, France;6. Health Information and Clinical Research, France;7. Hospices Civils de Lyon, Centre Hospitalier Lyon Sud Pierre Bénite, Department of Anaesthesiology, France;1. Centre de Recherche sur le Cancer, Université Laval and Département de Radio-Oncologie, Centre Hospitalier Universitaire de Québec, Québec, QC, Canada;2. Centre Intégré de Cancérologie de la Montérégie, Hôpital Charles-LeMoyne, Greenfield Park, QC, Canada;3. Department of Radiation Oncology Maastricht Radiation Oncology (MAASTRO), GROW, University Hospital Maastricht, Maastricht, The Netherlands;4. Gray Institute for Radiation Oncology and Biology, The University of Oxford, The United Kingdom;5. Medical Physics Unit, Department of Oncology, McGill University, Montréal, Québec, Canada;1. Inserm U953, Epidemiological Research Unit on Perinatal, Women’s and Children’s Health, Maternité de Port Royal, 53 Avenue de l’Observatoire, 75014 Paris, France;2. Université Paris Descartes, 12 rue de l’Ecole de Médecine, 75006 Paris, France;3. Université Paris Sud, 63 rue Gabriel Péri, 94276 Le Kremlin Bicêtre, France;4. Department of Pediatric and Adolescent Oncology, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France;5. Department of General Pediatrics, Hôpital Necker-Enfants Malades, AP-HP, 149 rue de Sèvres, 75015 Paris, France |
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| Abstract: | Prostate cancer is the most common malignancy in Western Europe, of which approximately 10–20% presents with advanced or metastatic disease. Initial response with androgen deprivation therapy is almost universal, but progression to castration resistant prostate cancer (CRPC), an incurable disease, occurs in approximately 2–3 years.In recent years, the novel taxane cabazitaxel, the hormonal agents abiraterone and enzalutamide, the immunotherapeutic agent sipuleucel-T and the radiopharmaceutical radium-223 have been shown to prolong survival in large randomised trials, thus widely increasing the therapeutic armamentarium against the disease. Despite these advances, the median survival in the first-line setting of metastatic castration-resistant prostate cancer (mCRPC) is still up to 25 months and in the post-docetaxel setting is about 15–18 months.There is an urgent need for the development of biomarkers of treatment response, and for a deeper understanding of tumour heterogeneity and the molecular biology underlying the disease. In this review, we attempt to provide insight into the novel molecular targets showing promise in clinical trials. |
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| Keywords: | Castration resistant prostate cancer Molecular biology Androgen receptor Novel therapeutics |
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