da Silva Henrique B, Amaral Eduardo P, Nolasco Eduardo L, de Victo Nathalia C, Atique Rodrigo, Jank Carina C, Anschau Valesca, Zerbini Luiz F, Correa Ricardo G
Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Avenida Prof. Lineu Prestes 1730, 05508-900 São Paulo, SP, Brazil.
Prostate Cancer. 2013;2013:920612. doi: 10.1155/2013/920612. Epub 2013 Apr 29.
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.
前列腺癌(PCa)是男性中最常见的恶性肿瘤之一。PCa的发展涉及前列腺上皮细胞中的多种突变,通常与发育变化相关,如对凋亡性死亡的抗性增强、持续性增殖,在某些情况下还与分化为雄激素剥夺抗性表型有关,从而导致去势抵抗性PCa(CRPCa)的出现,这会使患者预后不良。在本综述中,我们总结了有关导致PCa和/或CRPCa发展的主要信号通路失调的最新研究结果。某些通路分子中的关键突变通常与PCa的较高患病率相关,这是通过直接影响各自的级联反应,以及在某些情况下通过失调沿通路的串扰节点或连接点来实现的。我们还讨论了这些突变可能的环境和非环境诱导因素,以及针对这些信号通路的潜在治疗策略。更好地理解一些风险因素如何诱导这些信号通路失调,以及这些失调的通路如何影响PCa和CRPCa的发展,将进一步有助于开发针对这种疾病的新治疗方法和预防策略。