Villanueva Augusto, Toffanin Sara, Llovet Josep M
BCLC Group, Liver Unit, CIBERehd, IDIBAPS, Hospital Clinic, Barcelona, Spain.
Curr Opin Oncol. 2008 Jul;20(4):444-53. doi: 10.1097/CCO.0b013e328302c9e9.
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.
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.
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.
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。
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。
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。