肝癌异质性研究的现状和展望

Clonal heterogeneity and tumor evolution in liver cancer： the cutting edge and the future

肝癌被认为是异质性最强的肿瘤之一。肝癌的异质性包括肿瘤间异质性和肿瘤内异质性，两者既相互区别又紧密联系，其中既有遗传异质性又有微环境异质性。肿瘤异质性提示了＂单次活检所得的遗传特征和微环境信息＂的不足，它所强调的多样性和动态变化，对研究个体肝癌发展史、攻克耐药性及实现真正意义上的个体化精准治疗有着重要的理论价值和临床意义。

Human hepatocellular carcinoma （HCC） is a highly heterogeneous disease consisting of cells that differ in clinically important phenotypic features. This phenotypic heterogeneity, including intertumor heterogeneity and intratumor heterogeneity, is a result of the interplay between （epi） genetic and non-genetic microenvironmental factors that shape cellular phenotypes. Intratumor heterogeneity mandates understanding of longitudinal and spatial subclonal dynamics, and adds new levels of complexity in the molecular understanding of HCC, leading to primary and secondary resistance to targeted therapies. We believe that the recognition of the importance of intratumor heterogeneity combined with the rapid development of technologies allowing its interrogation will offer insight into therapy response, tumor evolutionary histories and clinical trial design in HCC.