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肝细胞癌(HCC)的分子诊断和治疗:先进技术的新兴领域。

Molecular diagnosis and therapy of hepatocellular carcinoma (HCC): an emerging field for advanced technologies.

机构信息

Department of Medicine I, Johannes Gutenberg University, Mainz, Germany.

出版信息

J Hepatol. 2012 Jan;56(1):267-75. doi: 10.1016/j.jhep.2011.07.007. Epub 2011 Jul 23.

Abstract

Despite great progress in diagnosis and management of hepatocellular carcinoma (HCC), the exact biology of the tumor remains poorly understood overall limiting the patients' outcome. Detailed analysis and characterization of the molecular mechanisms and subsequently individual prediction of corresponding prognostic traits would revolutionize both diagnosis and treatment of HCC and is the key goal of modern personalized medicine. Over the recent years systematic approaches for the analysis of whole tumor genomes and transcriptomes as well as epigenomes became affordable tools in translational research. This includes simultaneous analyses of thousands of molecular targets using microarray-based technologies as well as next-generation sequencing. Although currently diagnosis and classification of hepatocellular cancers still rely on histological examination of tumor sections, these technologies show great promise to advance the current knowledge of hepatocarcinogenesis, complement diagnostic classification in a setting of microarray-aided pathology, and rationalize the individual drug selection. This review aims to summarize recent progress of system biological approaches in hepatocarcinogenesis and outline potential areas for translational application in a clinical setting. Further, we give an update about known signaling pathways active in HCC, summarize the historical application of whole genomic approaches in liver cancer and indicate ongoing experimental research utilizing novel technologies in diagnosis and treatment of this deadly disease. This will also include the discussion and characterization of new molecular and cellular targets such as Cancer Stem Cells (CSCs).

摘要

尽管在肝细胞癌(HCC)的诊断和治疗方面取得了巨大进展,但肿瘤的确切生物学总体上仍了解甚少,这限制了患者的预后。详细分析和阐明分子机制,并随后对相应的预后特征进行个体化预测,将彻底改变 HCC 的诊断和治疗,这也是现代个性化医学的关键目标。近年来,用于分析整个肿瘤基因组、转录组和表观基因组的系统方法已成为转化研究中具有成本效益的工具。这包括使用基于微阵列的技术以及下一代测序同时分析数千个分子靶标。虽然目前肝细胞癌的诊断和分类仍依赖于肿瘤切片的组织学检查,但这些技术在推进肝癌发生的现有知识、在微阵列辅助病理学的背景下补充诊断分类以及合理化个体药物选择方面具有广阔的前景。本文旨在总结系统生物学方法在肝癌发生中的最新进展,并概述其在临床环境中的转化应用的潜在领域。此外,我们将更新 HCC 中活跃的已知信号通路的信息,总结全基因组方法在肝癌中的历史应用,并指出利用新技术在该致命疾病的诊断和治疗方面正在进行的实验研究。这还将包括对新的分子和细胞靶点(如癌症干细胞(CSC))的讨论和特征描述。

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