**1. Introduction**

#### **1.1. Pathophysiology of prostate cancer**

Considered part of both the male reproductive and urinary systems, the prostate gland (or prostate) is oval shaped, and is variable in size (ranging from 20 – 30 grams in adult males)[1]. The prostate gland consists of different types of cells, including gland (epithelial) cells, muscle cells and fibrous cells [2]. The overall structure of the prostate is divided in two ways: by zone, a classification more often used in pathology [2, 3] or by lobe, more often used in anatomy [2]. Prostate associated diseases usually present with urinary and sexual dysfunction and the initial symptoms related to such often necessitate diagnostic testing to indicate the presence of a certain disease state [4, 5]. Although the accuracy and use of Digital Rectal Examination (DRE) and Prostate Specific Antigen (PSA) remains controversial, these tests can be used alone, or in combination, to detect benign conditions (including benign prostatic hyperplasia (BPH) and prostatitis) or predict most forms of PCa [6, 7]. Subsequent prognosis of PCa is confirmed by prostate biopsy and involves pathological staging (Tumor/ Nodes/ Metastasis (TNM) System) and grading (Gleason Score) [8-10]. Broadly defined as the malignant growth of cells of the prostate gland, PCa occurs in many different zones of the prostate [1, 11, 12]. PCa (mostly 75%) arise in the peripheral zone, and to a lesser extent in the central and transitional zones [13]. Similar to the pattern of most epithelial cancers, cells within the prostate undergo an accumu‐ lation of genetic changes whereby the functions of cellular control are lost as the cell and tissue undergo phenotype changes from normal to prostatic intraepithelial neoplasia (PIN) [14]. This

© 2013 Tobin et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

progressively leads from to an acute high-grade PIN (HGPIN) to superficial cancers, and then to invasive disease [11, 12] (See Figure 1). The most common form of PCa (around 95%) originates in the glandular/epithelial tissue, and is coined prostatic adenocarcinoma; thus, this term has emerged synonymously with PCa [13]. The residual forms of PCa are termed nonadenocarcinoma, and present as less commonly occurring cancers, but are often more aggressive. Such can be categorized as epithelial (such as squamous cell carcinoma) and nonepithelial (such as osteo- and angio-sarcoma), and also include others which rarely develop in the prostate and are derived from primary tumors of the bladder and urethra (such as transitional cell carcinoma) [13]. The diagram below gives a general overview of prostate location, the division of zones and the general progression of PCa as the cell and tissue phenotype changes from normal to A. prostatic intraepithelial neoplasia (PIN), to B. increasing and severe high-grade PIN (HGPIN), then to C. superficial cancers, and finally to D. invasive disease [11, 12, 15].

**Figure 1.** GA Tobin, 2011. An Overview of the Pathogenesis of PCa.

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While the specific causes of PCa remain unknown, the only established risk factors for PCa are age, race and family history [16]. However, it is well accepted that the stimulation of androgens over a prolonged period contributes to the development of PCa [17]; thus, the androgen receptor (AR), along with its various cofactors play an important role in PCa. Nonetheless, progression of PCa to androgen independence (or the hormone refractory state) is one of the primary reasons for PCa-related deaths today [18]. PCa is the sixth most commonly diagnosed cancer worldwide [19]. For Canadian men, PCa is the most prevalent (based on 15 years) and frequently diagnosed non-dermatological cancer [20]. Like most other solid malignancies, PCa can extend to distant organs such as the liver, lungs and brain, with an abnormally high tendency for metastasizing to the bone [21, 22]. When distant metastasis occurs, the 5 year survival rate drops to 31% [20]. Although Prostate Specific Antigen (PSA) values, TNM staging, Gleason Score, and tumor biomarkers are considered significant in their ability to predict patient outcome, alone or when incorporated into various nomogram models, there is much controversy about their accuracy. Nonetheless, treatment regimens are largely based on these combined indicators.

Standard treatments for PCa can range from watchful waiting to surgery, radiation therapy, hormone therapy, chemotherapy, and biological therapy, alone or in combination [23-26]. Additionally, in North America, a minimum of 30% of men with diagnosed prostate disease choose to use complementary and/or alternative medical (CAM) therapy [27, 28] including primarily herbal biological agents, vitamins, supplements and dietary intervention [29]. This trend is likely due to progressive research on differences in global distribution, indicating that prolonged diet and micronutrient intake intervals may possibly control whether PCa remains latent or develops into a clinically significant disease [30-34]. In particular, the role of polyun‐ saturated fatty acids (PUFA) has gained considerable importance in PCa in the last several years. However, the molecular basis for these observations has not been fully explained. Genetic (and epigenetic) alterations and specific signaling pathways [35] are considered important in the multi-step process of cancer [36]. Thus, dietary interventions which target signaling pathways and downstream genes known to be impacted in PCa may be a worthwhile and effective approach in developing novel therapies.
