Hepatocellular carcinoma.
Hepatocellular carcinoma.
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DOI：
10.1038/s41572-020-00240-3
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发表时间：
2021-01-21
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肝癌仍然是一个全球性的健康挑战，到2025年估计发病率将达到100万例。肝细胞癌（HCC）是最常见的肝癌形式，约占90%的病例。乙型肝炎病毒和丙型肝炎病毒感染是HCC发展的主要危险因素，尽管与代谢综合征或糖尿病相关的非酒精性脂肪性肝炎在西方正成为更常见的危险因素。此外，非酒精性脂肪性肝炎相关的HCC具有独特的分子发病机制。大约25%的hcc存在潜在的可操作突变，这些突变尚未转化为临床实践。基于非侵入性标准的诊断目前受到需要组织或液体活检的分子信息的挑战。目前的主要进展影响了晚期HCC患者的管理。基于III期试验，已有6种全身疗法（atezolizumab + bevacizumab、sorafenib、lenvatinib、regorafenib、cabozantinib和ramucirumab）获得批准，另有3种疗法因疗效证据而获得FDA加速批准。新的试验正在探索联合疗法，包括检查点抑制剂和酪氨酸激酶抑制剂或抗vegf疗法，甚至是两种免疫疗法的组合。这些试验的结果有望改变HCC治疗在所有进化阶段的前景。
Liver cancer remains a global health challenge, with an estimated incidence of >1 million cases by 2025. Hepatocellular carcinoma (HCC) is the most common form of liver cancer and accounts for ~90% of cases. Infection by hepatitis B virus and hepatitis C virus are the main risk factors for HCC development, although non-alcoholic steatohepatitis associated with metabolic syndrome or diabetes mellitus is becoming a more frequent risk factor in the West. Moreover, non-alcoholic steatohepatitis-associated HCC has a unique molecular pathogenesis. Approximately 25% of all HCCs present with potentially actionable mutations, which are yet to be translated into the clinical practice. Diagnosis based upon non-invasive criteria is currently challenged by the need for molecular information that requires tissue or liquid biopsies. The current major advancements have impacted the management of patients with advanced HCC. Six systemic therapies have been approved based on phase III trials (atezolizumab plus bevacizumab, sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab) and three additional therapies have obtained accelerated FDA approval owing to evidence of efficacy. New trials are exploring combination therapies, including checkpoint inhibitors and tyrosine kinase inhibitors or anti-VEGF therapies, or even combinations of two immunotherapy regimens. The outcomes of these trials are expected to change the landscape of HCC management at all evolutionary stages.