Liver cancer is one of the most prevalent malignant tumors worldwide. According to the Barcelona Clinic Liver Cancer staging criteria, clinical guidelines provide tutorials to clinical management of liver cancer at their individual stages. However, most patients diagnosed with liver cancer are at advanced stage; therefore, many researchers conduct investigations on targeted therapy, aiming to improve the overall survival of these patients. To date, small-molecule-based targeted therapies are highly recommended (first line: sorafenib and lenvatinib; second line: regorafenib and cabozantinib) by current the clinical guidelines of the American Society of Clinical Oncology, European Society for Medical Oncology, and National Comprehensive Cancer Network. Herein, we summarize the small-molecule-based targeted therapies in liver cancer, including the approved and preclinical therapies as well as the therapies under clinical trials, and introduce their history of discovery, clinical trials, indications, and molecular mechanisms. For drug resistance, the revealed mechanisms of action and the combination therapies are also discussed. In fact, the known small-molecule-based therapies still have limited clinical benefits to liver cancer patients. Therefore, we analyze the current status and give our ideas for the urgent issues and future directions in this field, suggesting clues for novel techniques in liver cancer treatment.

中文翻译：

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肝癌中基于小分子的靶向治疗


肝癌是全球最普遍的恶性肿瘤之一。根据巴塞罗那临床肝癌分期标准，临床指南为肝癌的各个阶段的临床管理提供了教程。然而，大多数被诊断患有肝癌的患者已处于晚期;因此，许多研究人员对靶向治疗进行了调查，旨在提高这些患者的整体生存率。迄今为止，美国临床肿瘤学会、欧洲肿瘤内科学会和国家综合癌症网络的现行临床指南强烈推荐基于小分子的靶向治疗（一线：索拉非尼和仑伐替尼;二线：瑞戈非尼和卡博替尼）。本文总结了肝癌中基于小分子的靶向治疗，包括已批准的和临床前的治疗以及正在临床试验中的治疗，并介绍了它们的发现历史、临床试验、适应证和分子机制。对于耐药性，还讨论了揭示的作用机制和联合疗法。事实上，已知的基于小分子的疗法对肝癌患者的临床益处仍然有限。因此，我们分析了肝癌治疗的现状，并对该领域的紧迫问题和未来发展方向提出了自己的想法，为肝癌治疗的新技术提供了线索。