肝癌是一个全球性的健康挑战,造成重大的社会经济负担。肝细胞癌(HCC)是原发性肝癌的主要类型,在分子和细胞特征方面是高度异质的。早期或小肿瘤通常用手术或消融治疗。目前,化疗和免疫疗法是不可切除肿瘤或晚期HCC的最佳治疗方法。然而,药物反应和获得性耐药是不可预测的与现有的系统指南有关的突变模式和分子生物标志物,导致许多非典型分子谱患者的治疗结局不佳。凭借先进的技术平台,有价值的信息,如肿瘤遗传改变,表观遗传数据,和肿瘤微环境可以从液体活检获得。说明了肝癌的肿瘤间和肿瘤内异质性,这些数据为治疗方案的决策过程提供了坚实的证据.本文回顾了目前对HCC检测方法的理解,旨在更新使用液体活检进行HCC监测的发展。最近在分子基础上的重要发现,表观遗传概况,循环肿瘤细胞,循环DNA,和组学研究详细阐述了肝癌的诊断。此外,讨论了与治疗选择相关的生物标志物。还强调了一些最近关于靶向治疗的值得注意的临床试验。提供见解,将知识转化为潜在的生物标志物,用于检测和诊断。预后,治疗反应,以及在临床实践中的耐药指标。
Liver cancer is a global health challenge, causing a significant social-economic burden. Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer, which is highly heterogeneous in terms of molecular and cellular signatures. Early-stage or small tumors are typically treated with surgery or ablation. Currently, chemotherapies and
immunotherapies are the best treatments for unresectable tumors or advanced HCC. However, drug response and acquired resistance are not predictable with the existing systematic guidelines regarding mutation patterns and molecular biomarkers, resulting in sub-optimal treatment outcomes for many patients with atypical molecular profiles. With advanced technological platforms, valuable information such as tumor genetic alterations, epigenetic data, and tumor microenvironments can be obtained from liquid biopsy. The inter- and intra-tumoral heterogeneity of HCC are illustrated, and these collective data provide solid evidence in the decision-making process of treatment regimens. This article reviews the current understanding of HCC detection methods and aims to update the development of HCC surveillance using liquid biopsy. Recent critical findings on the molecular basis, epigenetic profiles, circulating tumor cells, circulating DNAs, and omics studies are elaborated for HCC diagnosis. Besides, biomarkers related to the choice of therapeutic options are discussed. Some notable recent clinical trials working on targeted therapies are also highlighted. Insights are provided to translate the knowledge into potential biomarkers for detection and diagnosis, prognosis, treatment response, and drug resistance indicators in clinical practice.