摘要
前列腺癌是男性最常见和最致命的癌症。大多数前列腺癌组织学上类似于腺泡的腺癌,并且它的发生和发展依靠雄激素信令。雄激素剥夺疗法是最主要的治疗方案,本文我们讨论最新雄激素阻断治疗方法。前列腺癌基因特征的最新研究已经表明,遗传异质性的深度超过了组织学中所看到的,并且我们有能力重新规定治疗方案。TMPRSS2-ETS家族融合蛋白是前列腺癌特有的蛋白,我们将讨论他们在癌变、预后过程中的作用,以及TMPRSS2-ETS家族基因融合的发展。失活的肿瘤抑制基因PTEN可导致PI3K / Akt / mTOR途径的激活,本文中我们将讨论它在预后和治疗的意义。最近的分子遗传分析表明,临床侵略性高级神经内分泌前列腺癌具有极光激酶和N-myc超表达的高发性。我们讨论极光激酶和N-myc对神经内分泌表型和特定基因亚型靶向抑制剂发展的作用。最后,我们简要讨论新兴的超表达体内定义的基因亚型:SPINK1、CHD1失活或SPOP突变。通过回顾前列腺癌的形态学与分子遗传学之间的关联特性,我们希望为新的靶向治疗提供指导。
关键词: 雄激素受体、分子细胞遗传学、神经内分泌/小细胞癌,个体化医学、前列腺癌、靶向治疗,TMPRSS2-ERG重排
Current Drug Targets
Title:Molecular Foundations for Personalized Therapy in Prostate Cancer
Volume: 16 Issue: 2
Author(s): Kurt W. Fisher, Rodolfo Montironi, Antonio Lopez Beltran, Holger Moch, Lisha Wang, Marina Scarpelli, Sean R. Williamson, Michael O. Koch and Liang Cheng
Affiliation:
关键词: 雄激素受体、分子细胞遗传学、神经内分泌/小细胞癌,个体化医学、前列腺癌、靶向治疗,TMPRSS2-ERG重排
摘要: Prostate cancer is the most common and second most lethal cancer in men. The majority of prostate cancers are histologically similar to acinar adenocarcinomas and rely on androgen-dependent signaling for their development and progression. Androgen deprivation therapy is a mainstay of treatment regimens and we discuss the recent advancements in androgen-deprivation therapy. Recent advances in defining the genetic landscape of prostate cancer have shown that the depth of genetic heterogeneity surpasses what can be seen histologically and has the ability to redefine treatments. TMPRSS2–ETS family fusion proteins are unique to prostate cancer and we discuss their role in carcinogenesis, prognosis, and the development of TMPRSS2–ETS family gene fusion targeted therapy. Inactivation of the tumor suppressor PTEN leads to activation of the PI3K/Akt/mTOR pathway and we discuss the prognostic and treatment implications. Molecular genetic analysis has recently demonstrated that clinically aggressive high grade neuroendocrine prostate carcinomas contain a high prevalence of overexpression of Aurora A kinase and N-myc. We discuss the role of Aurora A kinase and N-myc in the development of the aggressive neuroendocrine phenotype and the development of targeted inhibitors of this specific genetic subtype. Lastly, we briefly discuss emerging genetic subtypes defined by either SPINK1 overexpression, CHD1 inactivation, or SPOP mutations. By reviewing the associations between the morphologic features and the molecular genetics of prostate cancer we hope to provide insight and guidance to the emerging options for targeted therapy.
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Kurt W. Fisher , Rodolfo Montironi , Antonio Lopez Beltran , Holger Moch , Lisha Wang , Marina Scarpelli , Sean R. Williamson , Michael O. Koch and Liang Cheng , Molecular Foundations for Personalized Therapy in Prostate Cancer, Current Drug Targets 2015; 16 (2) . https://dx.doi.org/10.2174/1389450115666141229154500
DOI https://dx.doi.org/10.2174/1389450115666141229154500 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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