Prostate cancer (PCa) is one of the most common malignancies found in males. The development of PCa involves several mutations in prostate epithelial cells, usually linked to developmental changes, such as enhanced resistance to apoptotic death, constitutive proliferation, and, in some cases, to differentiation into an androgen deprivation-resistant phenotype, leading to the appearance of castration-resistant PCa (CRPCa), which leads to a poor prognosis in patients. In this review, we summarize recent findings concerning the main deregulations into signaling pathways that will lead to the development of PCa and/or CRPCa. Key mutations in some pathway molecules are often linked to a higher prevalence of PCa, by directly affecting the respective cascade and, in some cases, by deregulating a cross-talk node or junction along the pathways. We also discuss the possible environmental and nonenvironmental inducers for these mutations, as well as the potential therapeutic strategies targeting these signaling pathways. A better understanding of how some risk factors induce deregulation of these signaling pathways, as well as how these deregulated pathways affect the development of PCa and CRPCa, will further help in the development of new treatments and prevention strategies for this disease. 1. Introduction The long-term ineffectiveness of current treatments for prostate cancer (PCa) has spurred an increasing interest in understanding the molecular mechanisms that underlie PCa tumorigenesis [1]. Currently, PCa is considered the most common nonmelanoma neoplasia among men [2–4]. According to the current trends in population growth, the incidence of PCa will exceed 1.7 million new cases by 2030 [5]. In the United States, nearly 2.8 million men are potentially living with this condition, and approximately 240,000 new cases were diagnosed in 2012 [3]. PCa predominately affects elderly men with higher incidence [6], and it is more prevalent in Western countries [7], where the average life expectation is over 75 years old. In developing countries like Brazil, PCa has recently surpassed the population incidence of breast cancer, and it has become the most common tumor malignancy, with approximately 50,000 new cases occurring per year [4, 5]. Yet, there is a considerable heterogeneity in the mortality rates and incidence among different countries, probably due to the variable penetrance of some risk factors such as age, race, genetics (family history), diet and environmental factors [8], and also behavioral factors, like frequent consumption of dairy products and meat
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