Targeted therapy for hepatocellular carcinoma: Challenges and opportunities
Targeted therapy for hepatocellular carcinoma: Challenges and opportunities
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肝细胞癌靶向治疗：挑战与机遇
DOI：
10.1016/j.canlet.2019.114428
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发表时间：
2019-01-01
期刊：
影响因子：
9.7
通讯作者：
Wang, Hongyang
中科院分区：
文献类型：
--
作者：
Chen, Shuzhen;Cao, Qiqi;Wang, Hongyang
肝细胞癌（Hepatocellular carcinoma，HCC）是世界范围内最常见的恶性肿瘤之一，居恶性肿瘤死亡的第六位。尽管出现了靶向治疗，但由于低应答率和治疗耐药性，晚期HCC在很大程度上仍然无法治愈。本文就多激酶抑制剂和免疫治疗在肝癌治疗中的应用进展作一综述。我们强调了这些靶向治疗无效的机制，包括驱动基因和下游通路的致癌改变，HCC的高度异质性，以及肿瘤微环境的相互作用，促进治疗耐药性。我们还讨论了这些先前的研究如何建议未来的治疗策略。此外，HCC异质性和癌症革命的复杂性需要在个体化治疗中得到认识。建立一个药物筛选系统和确定反应的生物标志物也是克服耐药性的迫切需要。同时，靶向治疗的组合也可以作为未来有前途的策略进行探索。
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, which ranks as the sixth of cancer-related death. Despite the emergence of targeted therapy, advanced-stage HCC remains largely incurable due to low response rate and therapeutic resistance. In this review, we mainly focused on the current progression of multi-kinase inhibitors and immunotherapies in the treatment of HCC. We highlight the mechanism underlying the ineffectiveness of these targeted therapies, including oncogenic alterations in driver genes and downstream pathways, high heterogeneity of HCC, and the mutual interaction of tumor microenvironment that promotes therapeutic resistance. We also discussed how these previous studies suggested for future therapeutic strategies. Besides, the complexity of HCC heterogeneity and cancer revolution need to be recognized in personalized therapy. Establishment of a drug screening system and identification of biomarkers of response is also in urgent need to overcome drug resistance. Meanwhile, a combination of targeted therapies could also be explored as a promising strategy in the future.