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Molecular biology of prostate cancer

Donald Vander Griend, PhD
Section Editors
Nicholas Vogelzang, MD
W Robert Lee, MD, MS, MEd
Jerome P Richie, MD, FACS
Deputy Editor
Michael E Ross, MD


Prostate cancer is the second most common cancer in men worldwide, with an estimated 1,600,000 cases and 366,000 deaths in 2015 [1]. If completely localized within the capsule of the gland, some favorable-risk prostate cancers can be managed with active surveillance or potentially cured by definitive local therapy (eg, radical prostatectomy, radiation therapy, brachytherapy). In contrast, non-organ-confined disease is often fatal. (See "Initial approach to low- and very low-risk clinically localized prostate cancer" and "Overview of the treatment of disseminated castration-sensitive prostate cancer".)

Here we will provide an overview of the molecular changes that are proposed to be involved in the initiation and progression of prostate cancer, particularly those that accompany metastatic disease and castration resistance. The diagnosis, staging, and treatment of prostate cancer are covered elsewhere. (See appropriate topic reviews).


Metastatic prostate cancers can be lethal because they heterogeneously contain both androgen-dependent and androgen-independent malignant cells. For those cells that are androgen dependent, a critical level of androgen is required to activate a sufficient number of androgen receptors (ARs) so that transcription of death-signaling genes is expressed [2]. Androgen ablation therapies allow these genes to be repressed, triggering the biochemical cascade that results in apoptotic cell death, resulting in the eradication of the large fraction of androgen-dependent cancer cells [3,4]. In contrast, androgen ablation does not induce apoptosis in androgen-independent cells [5]; their eventual outgrowth is responsible for the lethality of advanced disease. (See "Overview of the treatment of disseminated castration-sensitive prostate cancer".)

Although prostate cancer typically presents in men over the age of 65, a growing body of evidence suggests that prostatic carcinogenesis is initiated much earlier [6]. Prostatic intraepithelial neoplasia (PIN) is thought to represent a precursor of adenocarcinoma, although not all cases progress to invasive disease. One of the most pressing clinical problems presented by prostate cancer is the difficulty in predicting its clinical course based upon clinical or histologic features. (See "Precancerous lesions of the prostate: Pathology and clinical implications".)

Prostate cancer progression has been related to a number of genetic abnormalities that affect the AR and other molecules that are involved in the regulation of cell survival and apoptosis [7]. A multistep process of prostate carcinogenesis has been proposed in which progressive accumulation of genetic alterations is postulated to facilitate cellular transformation from normal prostate epithelium to PIN, invasive neoplasia, and castration resistance [7,8].

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Literature review current through: Nov 2017. | This topic last updated: Apr 14, 2017.
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