Marin Jose J G, Macias Rocio I R, Monte Maria J, Romero Marta R, Asensio Maitane, Sanchez-Martin Anabel, Cives-Losada Candela, Temprano Alvaro G, Espinosa-Escudero Ricardo, Reviejo Maria, Bohorquez Laura H, Briz Oscar
Experimental Hepatology and Drug Targeting (HEVEFARM) Group, University of Salamanca, IBSAL, 37007 Salamanca, Spain.
Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, 28029 Madrid, Spain.
Cancers (Basel). 2020 Jun 23;12(6):1663. doi: 10.3390/cancers12061663.
The poor outcome of patients with non-surgically removable advanced hepatocellular carcinoma (HCC), the most frequent type of primary liver cancer, is mainly due to the high refractoriness of this aggressive tumor to classical chemotherapy. Novel pharmacological approaches based on the use of inhibitors of tyrosine kinases (TKIs), mainly sorafenib and regorafenib, have provided only a modest prolongation of the overall survival in these HCC patients. The present review is an update of the available information regarding our understanding of the molecular bases of mechanisms of chemoresistance (MOC) with a significant impact on the response of HCC to existing pharmacological tools, which include classical chemotherapeutic agents, TKIs and novel immune-sensitizing strategies. Many of the more than one hundred genes involved in seven MOC have been identified as potential biomarkers to predict the failure of treatment, as well as druggable targets to develop novel strategies aimed at increasing the sensitivity of HCC to pharmacological treatments.
不可手术切除的晚期肝细胞癌（HCC）是原发性肝癌最常见的类型，这类患者预后较差，主要是因为这种侵袭性肿瘤对传统化疗具有高度难治性。基于使用酪氨酸激酶抑制剂（TKIs），主要是索拉非尼和瑞戈非尼的新型药理学方法，仅使这些HCC患者的总生存期略有延长。本综述是关于我们对化疗耐药机制（MOC）分子基础的理解的现有信息的更新，这些机制对HCC对现有药理学工具（包括传统化疗药物、TKIs和新型免疫致敏策略）的反应有重大影响。参与七种MOC的一百多个基因中的许多已被确定为预测治疗失败的潜在生物标志物，以及开发旨在提高HCC对药物治疗敏感性的新策略的可成药靶点。
