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Molecular biology of prostate cancer

Author
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

INTRODUCTION

Prostate cancer is the second most common cancer in men worldwide, with an estimated 1,100,000 cases and 307,000 deaths in 2012 [1]. If completely localized within the capsule of the gland, prostate cancer can usually be cured by definitive local therapy such as radical prostatectomy or radiation therapy. 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 prostate cancer".)

Metastatic prostate cancers can be lethal because they are heterogeneously composed of 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 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 androgen receptor (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].

Over the last decade, a number of genes involved in or associated with prostate cancer have been identified and characterized [7]. Many of these genes or their protein products are under study for their value in clinical staging (sometimes termed "molecular staging") with the goal of more closely tailoring the selection of treatment to expected prognosis [9]. Perhaps more importantly, mechanistic studies to determine the biochemical result of specific molecular changes might reveal additional targets for therapy. Unfortunately, the heterogeneity of prostate cancers, the variability in analytic techniques, and the lack of suitable model systems for different stages of in prostate progression have hampered progress. (See "Clinical presentation and diagnosis of prostate cancer".)

                            

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Literature review current through: Nov 2016. | This topic last updated: Tue Jul 21 00:00:00 GMT+00:00 2015.
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