摘要
Prostate cancer （PCa） incidence and mortality have decreased in recent years. Nonetheless, it remains one of the most prevalent cancers in men, being a disquieting cause of men＇s death worldwide. Changes in many cell signaling pathways have a predominant role in the onset, development, and progression of the disease. These include prominent pathways involved in the growth, apoptosis, and angiogenesis of the normal prostate gland, such as an- drogen and estrogen signaling, and other growth factor signaling pathways. Understanding the foundations of PCa is leading to the discovery of key molecules that could be used to improve patient management. The ideal scenario would be to have a panel of molecules, preferably detectable in body fluids, that are specific and sensitive biomarkers for PCa In the early stages, androgen deprivation is the gold standard therapy. However, as the cancer progresses, it even- tually becomes independent of androgens, and hormonal therapy fails. For this reason, androgen-independent PCa is still a major therapeutic challenge. By disrupting specific protein interactions or manipulating the expression of some key molecules, it might be possible to regulate tumor growth and metastasis formation, avoiding the systemic side effects of current therapies. Clinical trials are already underway to assess the efficacy of molecules specially designed to target key proteins or protein interactions. In this review, we address that recent progress made towards under- standing PCa development and the molecular pathways underlying this pathology. We also discuss relevant molecular markers for the management of PCa and new therapeutic challenges.
研究目的:这篇综述系统地阐述了前列腺癌的发生、发展、相关分子信号通路以及分子标志物用于前列腺癌的临床诊断和前列腺癌诊治所面临的挑战。重要结论:许多分子信号通路通过影响细胞生长、凋亡、血管生成等病理生理过程而参与了前列腺癌的起始、发生和发展。这些研究基础有助于寻找前列腺癌的肿瘤标志物和改进前列腺癌的治疗。虽然去势治疗是早期前列腺癌治疗的金标准,但是晚期的激素抵抗型前列腺癌(CRPC)的治疗仍面临着巨大的挑战。所幸的是,目前研究发现可以通过切断特异的蛋白-蛋白相互作用或者通过调节某些影响肿瘤生长和转移的关键分子来治疗前列腺癌,能减少传统治疗所带来的副作用;相关临床研究已开始实施。这些研究进展给前列腺癌的诊治带来了新的曙光。
基金
Project supported by Fundao para a Ciência e Tecnologia(FCT)(PTDC/QUI-BIQ/118492/2010)
Fundo Europeu de Desenvol-vimento Regional(FEDER)(FCOMP-01-0124-FEDER-020895),Portugal
