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Focal gains of VEGFA and molecular classification of hepatocellular carcinoma.VEGFA的局灶性增加与肝细胞癌的分子分类
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Design and endpoints of clinical trials in hepatocellular carcinoma.肝细胞癌临床试验的设计与终点
J Natl Cancer Inst. 2008 May 21;100(10):698-711. doi: 10.1093/jnci/djn134. Epub 2008 May 13.
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Genetically distinct and clinically relevant classification of hepatocellular carcinoma: putative therapeutic targets.肝细胞癌的基因不同且与临床相关的分类:假定的治疗靶点。
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Newly revealed genome complexity may mean personalized medicine is farther away.
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Personalized medicine in the era of genomics.基因组学时代的个性化医疗。
JAMA. 2007 Oct 10;298(14):1682-4. doi: 10.1001/jama.298.14.1682.
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Phase III randomized controlled trial comparing the survival of patients with unresectable hepatocellular carcinoma treated with nolatrexed or doxorubicin.一项比较接受诺拉曲塞或阿霉素治疗的不可切除肝细胞癌患者生存率的III期随机对照试验。
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Phase 2 study of erlotinib in patients with unresectable hepatocellular carcinoma.厄洛替尼用于不可切除肝细胞癌患者的2期研究。
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Phase 2 study of cetuximab in patients with advanced hepatocellular carcinoma.西妥昔单抗用于晚期肝细胞癌患者的2期研究。
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Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma.丙型肝炎病毒诱导的发育异常和肝细胞癌的全基因组分子图谱。
Hepatology. 2007 Apr;45(4):938-47. doi: 10.1002/hep.21622.
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肝细胞癌的分子分类与个性化医疗的关联:初步步骤

Linking molecular classification of hepatocellular carcinoma and personalized medicine: preliminary steps.

作者信息

Villanueva Augusto, Toffanin Sara, Llovet Josep M

机构信息

BCLC Group, Liver Unit, CIBERehd, IDIBAPS, Hospital Clinic, Barcelona, Spain.

出版信息

Curr Opin Oncol. 2008 Jul;20(4):444-53. doi: 10.1097/CCO.0b013e328302c9e9.

DOI:10.1097/CCO.0b013e328302c9e9
PMID:18525342
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3678124/
Abstract

PURPOSE OF REVIEW

The development of high-throughput technologies able to simultaneously investigate thousands of genes (e.g. single nucleotide polymorphism-array, gene expression microarray, etc.) has opened a new era in translational research. Obtaining a molecular classification of hepatocellular carcinoma, however, remains a striking challenge. This review summarizes the molecular classifications of hepatocellular carcinoma reported so far, analyzes the status of targeted therapies tested in clinical trials, and evaluates feasibility of personalized medicine approaches in hepatocellular carcinoma.

RECENT FINDINGS

Different investigators attempted to classify patients according to their liver cancer molecular background, a feature that will path the way for trial enrichment and personalized medicine. Currently, hepatocellular carcinoma can be classified in molecular classes according to Wnt-beta-catenin pathway activation, proliferation signature activation (associated with chromosomal instability), and other subgroups. In parallel, the first-time-ever positive results of a phase III trial in advanced hepatocellular carcinoma with the multikinase inhibitor sorafenib have encouraged this approach.

SUMMARY

Selection of patient candidates according to their tumor molecular background is a reality in human malignancies. Thus, a molecular classification is essential to allow the development of new targets, and to customize therapies in patients with hepatocellular carcinoma.

摘要

综述目的

能够同时研究数千个基因的高通量技术(如单核苷酸多态性阵列、基因表达微阵列等)的发展开启了转化研究的新时代。然而,获得肝细胞癌的分子分类仍然是一个巨大的挑战。本综述总结了目前已报道的肝细胞癌分子分类,分析了在临床试验中测试的靶向治疗的现状,并评估了肝细胞癌个性化医疗方法的可行性。

最新发现

不同的研究人员试图根据患者的肝癌分子背景对患者进行分类,这一特征将为试验富集和个性化医疗铺平道路。目前,肝细胞癌可根据Wnt-β-连环蛋白通路激活、增殖特征激活(与染色体不稳定性相关)及其他亚组进行分子分类。同时,多激酶抑制剂索拉非尼在晚期肝细胞癌III期试验中首次取得的阳性结果推动了这种方法的发展。

总结

根据肿瘤分子背景选择候选患者在人类恶性肿瘤中已成为现实。因此,分子分类对于开发新靶点以及为肝细胞癌患者定制治疗方案至关重要。