Sun Hang, Yang Huayu, Mao Yilei
Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, Peking Union Medical College (PUMC) and Chinese Academy of Medical Sciences (CAMS), Beijing, China.
Front Pharmacol. 2023 May 5;14:1150151. doi: 10.3389/fphar.2023.1150151. eCollection 2023.
Hepatocellular carcinoma (HCC) is a major global health burden, causing approximately 8.3 million deaths each year, and it is the third leading cause of cancer-related death worldwide, with a relative 5-year survival rate of around 18%. Due to the advanced stage of diagnosis in most patients, systemic treatment based on targeted therapy has become the only feasible option. Genomic studies have established a profile of molecular alterations in hepatocellular carcinoma with potentially actionable mutations, but these mutations have yet to be translated into clinical practice. The first targeted drug approved for systemic treatment of patients with advanced hepatocellular carcinoma was Sorafenib, which was a milestone. Subsequent clinical trials have identified multiple tyrosine kinase inhibitors, such as Lenvatinib, Cabozantinib, and Regorafenib, for the treatment of hepatocellular carcinoma, with survival benefits for the patient. Ongoing systemic therapy studies and trials include various immune-based combination therapies, with some early results showing promise and potential for new therapy plans. Systemic therapy for hepatocellular carcinoma is complicated by the significant heterogeneity of the disease and its propensity for developing drug resistance. Therefore, it is essential to choose a better, individualized treatment plan to benefit patients. Preclinical models capable of preserving tumor characteristics are urgently needed to circumvent heterogeneity and overcome drug resistance. In this review, we summarize current approaches to targeted therapy for HCC patients and the establishment of several patient-derived preclinical models of hepatocellular carcinoma. We also discuss the challenges and opportunities of targeted therapy for hepatocellular carcinoma and how to achieve personalized treatment with the continuous development of targeted therapies and bioengineering technologies.
肝细胞癌（HCC）是一项重大的全球健康负担，每年导致约830万人死亡，是全球癌症相关死亡的第三大原因，相对5年生存率约为18%。由于大多数患者诊断时已处于晚期，基于靶向治疗的全身治疗已成为唯一可行的选择。基因组研究已确定了肝细胞癌中具有潜在可操作突变的分子改变特征，但这些突变尚未转化为临床实践。首个被批准用于晚期肝细胞癌患者全身治疗的靶向药物是索拉非尼，这是一个里程碑。随后的临床试验确定了多种酪氨酸激酶抑制剂，如乐伐替尼、卡博替尼和瑞戈非尼，用于治疗肝细胞癌，给患者带来了生存益处。正在进行的全身治疗研究和试验包括各种基于免疫的联合疗法，一些早期结果显示出对新治疗方案的希望和潜力。肝细胞癌的全身治疗因疾病的显著异质性及其产生耐药性的倾向而变得复杂。因此，选择更好的个体化治疗方案以使患者受益至关重要。迫切需要能够保留肿瘤特征的临床前模型来规避异质性并克服耐药性。在本综述中，我们总结了目前针对HCC患者的靶向治疗方法以及几种患者来源的肝细胞癌临床前模型的建立。我们还讨论了肝细胞癌靶向治疗的挑战和机遇，以及随着靶向治疗和生物工程技术的不断发展如何实现个性化治疗。
