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前列腺癌分子图谱:精准医学实施的致命弱点。

Prostate cancer molecular profiling: the Achilles heel for the implementation of precision medicine.

作者信息

Oliveira-Barros Eliane Gouvêa, Nicolau-Neto Pedro, Da Costa Nathalia Meireles, Pinto Luís Felipe Ribeiro, Palumbo Antonio, Nasciutti Luiz Eurico

机构信息

Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, CEP: 21941-902, Rio de Janeiro, Brazil.

Programa de Carcinogênese Molecular, Centro de Pesquisas (CPQ), Instituto Nacional de Câncer (INCA), Rua André Cavalcanti, 37-Centro, CEP: 20231-050, Rio de Janeiro, Brazil.

出版信息

Cell Biol Int. 2017 Nov;41(11):1239-1245. doi: 10.1002/cbin.10785. Epub 2017 May 18.

Abstract

Cancer has been mainly treated by traditional therapeutic approaches which do not consider the human genetic diversity and present limitations, probably as a consequence of a poor knowledge of both patient's genetic background and tumor biology. Due to genome project conclusion and large-scale gene analyses emergence, the therapeutic management of several prevalent and aggressive tumors has dramatically improved and represents the closest examples of a precision medicine intervention in this field. Nonetheless, prostate cancer (PCa) remains as a challenge to personalized medicine implementation, probably due to its notorious heterogeneous molecular profile. Cancer treatment personalized approaches rely on the premise that a well-defined panorama of tumor molecular alterations can help selecting new and specific therapeutic targets for its treatment and potentially discriminate tumors which behave differentially. Lately, molecular and genetic studies have been investigating PCa basis, revealing multiple recurrent genomic alterations that include mutations, DNA copy-number variations, rearrangements, and gene fusions, among others. In addition to the increment on PCa molecular biology knowledge, mapping the molecular alterations pattern of this neoplasia, especially the differences existent between tumors displaying distinct behaviors, could represent a great improvement concerning the identification of new targets, personalized medicine, and patients' management and prognosis.

摘要

癌症主要通过传统治疗方法进行治疗,这些方法没有考虑人类基因多样性且存在局限性,这可能是由于对患者基因背景和肿瘤生物学了解不足所致。由于基因组计划的完成和大规模基因分析的出现,几种常见侵袭性肿瘤的治疗管理有了显著改善,这是该领域精准医学干预最典型的例子。尽管如此,前列腺癌(PCa)仍然是个性化医疗实施的一个挑战,这可能是由于其众所周知的分子特征异质性。癌症治疗的个性化方法基于这样一个前提,即明确的肿瘤分子改变全景有助于选择新的特定治疗靶点,并有可能区分行为不同的肿瘤。最近,分子和基因研究一直在探究前列腺癌的基础,揭示了多种常见的基因组改变,包括突变、DNA拷贝数变异、重排和基因融合等。除了前列腺癌分子生物学知识的增加外,绘制这种肿瘤的分子改变模式,特别是不同行为肿瘤之间存在的差异,可能在新靶点识别、个性化医疗以及患者管理和预后方面带来巨大改善。

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