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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肝癌的小分子靶向治疗


肝癌是全世界最常见的恶性肿瘤之一。根据巴塞罗那临床肝癌分期标准，临床指南为肝癌各个阶段的临床管理提供了教程。然而，大多数被诊断出肝癌的患者已处于晚期阶段；因此，许多研究人员对靶向治疗进行研究，旨在提高这些患者的总体生存率。迄今为止，美国临床肿瘤学会、欧洲肿瘤内科学会和美国国家综合肿瘤协会的临床指南强烈推荐基于小分子的靶向治疗（一线：索拉非尼和乐伐替尼；二线：瑞戈非尼和卡博替尼）。癌症网络。在此，我们总结了肝癌的小分子靶向治疗，包括已批准的、临床前的治疗以及正在进行临床试验的治疗，并介绍了它们的发现历史、临床试验、适应症和分子机制。对于耐药性，还讨论了已揭示的作用机制和联合疗法。事实上，已知的小分子疗法对肝癌患者的临床益处仍然有限。因此，我们分析了该领域的现状，并对该领域的紧迫问题和未来方向提出了自己的想法，为肝癌治疗的新技术提供了线索。