Hepatocellular carcinoma
Hepatocellular carcinoma
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DOI：
10.1038/nrdp.2016.18
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发表时间：
2016-04-14
影响因子：
81.5
通讯作者：
Gores, Gregory
中科院分区：
文献类型：
--
作者：
Llovet, Josep M.;Zucman-Rossi, Jessica;Gores, Gregory
肝癌是全球癌症相关死亡的第二大原因，每年约有850，000例新发病例。肝细胞癌（HCC）占所有原发性肝癌病例的约90%。发生HCC的主要危险因素是众所周知的，包括B和C型肝炎病毒感染、酒精摄入和真菌代谢物黄曲霉毒素B1的摄入。其他风险因素，如非酒精性脂肪性肝炎也正在出现。对HCC分子发病机制的理解的进展已经导致了关键驱动突变的鉴定;然而，这些突变中最普遍的尚未成为药物靶点。HCC的分子分类尚未建立，巴塞罗那临床肝癌分期分类是根据预后和治疗分配对患者进行分层的主要临床算法。监测项目能够检测出适合治愈性治疗的早期肿瘤切除、肝移植或局部消融。在更发展的阶段，只有化疗栓塞（用于中期HCC）和索拉非尼（用于晚期HCC）显示出生存益处。HCC管理中存在主要未满足的需求，可以通过发现新的治疗方法及其组合用于辅助治疗和中晚期疾病来解决。此外，需要用于治疗分层的生物标志物、针对驱动突变和/或激活信号级联的患者定制策略以及经验证的生活质量测量。最近在中期和晚期的系统性药物试验中的失败表明需要改进试验设计和确定新的方法。
Liver cancer is the second leading cause of cancer-related deaths globally and has an incidence of approximately 850,000 new cases per year. Hepatocellular carcinoma (HCC) represents approximately 90% of all cases of primary liver cancer. The main risk factors for developing HCC are well known and include hepatitis B and C virus infection, alcohol intake and ingestion of the fungal metabolite aflatoxin B1. Additional risk factors such as non-alcoholic steatohepatitis are also emerging. Advances in the understanding of the molecular pathogenesis of HCC have led to identification of critical driver mutations; however, the most prevalent of these are not yet druggable targets. The molecular classification of HCC is not established, and the Barcelona Clinic Liver Cancer staging classification is the main clinical algorithm for the stratification of patients according to prognosis and treatment allocation. Surveillance programmes enable the detection of early-stage tumours that are amenable to curative therapies-resection, liver transplantation or local ablation. At more developed stages, only chemoembolization (for intermediate HCC) and sorafenib (for advanced HCC) have shown survival benefits. There are major unmet needs in HCC management that might be addressed through the discovery of new therapies and their combinations for use in the adjuvant setting and for intermediate-and advanced-stage disease. Moreover, biomarkers for therapy stratification, patient-tailored strategies targeting driver mutations and/ or activating signalling cascades, and validated measurements of quality of life are needed. Recent failures in the testing of systemic drugs for intermediate and advanced stages have indicated a need to refine trial designs and to define novel approaches.