%0 Journal Article
%T Castration-Resistant Prostate Cancer: Mechanisms, Targets, and Treatment
%A Teresa Maria Santos Amaral
%A Daniela Macedo
%A Isabel Fernandes
%A Luis Costa
%J Prostate Cancer
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/327253
%X Patients with castration-resistant prostate cancer (CRPC), who progress after docetaxel therapy, had until very recently, only a few therapeutic options. Recent advances in this field brought about new perspectives in the treatment of this disease. Molecular, basic, and translational research has given us a better understanding on the mechanisms of CRPC. This great investment has turned into a more rational approach to the development of new drugs. Some of the new treatments are already available to our patients outside clinical trials and may include inhibitors of androgen biosynthesis; new chemotherapy agents; bone-targeted therapy; and immunotherapy. This paper aims to review the mechanisms of prostate cancer resistance, possible therapeutic targets, as well as new options to treat CRPC. 1. Introduction Prostate cancer is the most common malignancy in males in Western countries, representing the second leading cause of cancer death [1]. Advances in screening and diagnosis have allowed detection of the disease in early stages (approximately 85% of cases diagnosed), stages at which the therapeutic options are curative and include surgery, radiation and, in some cases, active surveillance only [2¨C4]. However, for late-stage disseminated disease, current therapies are merely palliative. In 1941, a study of Huggins and Hodges showed the close relationship of androgens with prostate tumor growth and androgen-deprivation therapy (castration) became the key treatment for these stages in monotherapy or in combination with other methods [2, 4, 5]. Initial responses to castration therapy are quite favorable, with a significant clinical regression and rapid biochemical responses, as assessed by decline in levels of serum marker, prostate-specific antigen (PSA) in 80¨C90% of patients with metastatic disease [2, 4, 6]. Despite a good initial response, remissions last on average 2-3 years, with eventual progression occurring despite castration [4, 5, 7]. In these cases prostate cancer will progress to a castration-insensitive phase of disease (Castration-Resistant Prostate Cancer¡ªCRPC) which carries a worse prognosis and translates into a survival time of 16¨C18 months in average from the beginning of progression [2, 4¨C6]. Systemic therapies have also been an option in the management to these patients. However, chemotherapy is not well tolerated by all CRPC patients, who were often elderly men with limited bone marrow reserve and concurrent medical conditions [8]. In 2004 the result of two major phase 3 clinical trials established docetaxel as the first-line
%U http://www.hindawi.com/journals/pc/2012/327253/