title: Progress in the treatment of advanced prostate cancer.
abstract: The androgen receptor (AR) is the most significant target for patients with metastatic castration-resistant prostate cancer (mCRPC). There is now irrefutable evidence that the AR axis is functional in most patients throughout the history of prostate cancer, is crucial from diagnosis to death, even in patients who have received hormonal manipulation, and represents a relevant therapeutic target in all phases of the disease. The potential mechanisms of tumor escape after castration are multifold, with each mechanism today representing a therapeutic opportunity. Phase III trials have been able to demonstrate improved overall survival (OS), improved quality of life, decreased skeletal-related events, and other important clinical benefits in young and elderly patients. After the initial positive results with docetaxel chemotherapy in improving OS, further research has resulted in five new treatments in the past few years. Immunotherapy with sipuleucel-T, cabazitaxel chemotherapy, the androgen biosynthesis inhibitor abiraterone acetate, the antiandrogen enzalutamide, and the radioisotope radium-223 have all been shown to improve OS in large-scale, well-conducted clinical trials. Proper understanding of mechanisms of resistance and of cross-resistance among these agents, sequencing, and combinations is now a priority.
authors.affiliation: From the San Camillo Forlanini Hospital, Rome, Italy; Yale University Cancer Center, New Haven, CT; Center for Cancer Research, National Cancer Institute, Bethesda, MD; The Royal Marsden Hospital, London, United Kingdom.
authors.forename: Cora N
authors.initials: CN
authors.lastname: Sternberg
authors.affiliation: From the San Camillo Forlanini Hospital, Rome, Italy; Yale University Cancer Center, New Haven, CT; Center for Cancer Research, National Cancer Institute, Bethesda, MD; The Royal Marsden Hospital, London, United Kingdom.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Petrylak
authors.affiliation: From the San Camillo Forlanini Hospital, Rome, Italy; Yale University Cancer Center, New Haven, CT; Center for Cancer Research, National Cancer Institute, Bethesda, MD; The Royal Marsden Hospital, London, United Kingdom.
authors.forename: Ravi A
authors.initials: RA
authors.lastname: Madan
authors.affiliation: From the San Camillo Forlanini Hospital, Rome, Italy; Yale University Cancer Center, New Haven, CT; Center for Cancer Research, National Cancer Institute, Bethesda, MD; The Royal Marsden Hospital, London, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Parker
mesh_terms: D000726:Androgen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009919:Orchiectomy / Q000009:adverse effects; D011471:Prostatic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use*; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: C410798:AR protein, human; D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D019275:Radiopharmaceuticals; D011944:Receptors, Androgen