

FOLLOWUS
Department of Gastroenterology, the Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan Province 421002, China
* Xuefeng Yang, E-mail: yxf9988@126.com
Received:06 March 2020,
Accepted:2020-5-11,
Published Online:31 March 2021,
Published:31 March 2021
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Chen Qiong, Yang Xuefeng. Research Progress in Targeted Therapy of Hepatocellular Carcinoma[J]. Chinese medical sciences journal, 2021, 36(1): 57-65.
Chen Qiong, Yang Xuefeng. Research Progress in Targeted Therapy of Hepatocellular Carcinoma[J]. Chinese medical sciences journal, 2021, 36(1): 57-65. DOI: 10.24920/003737.
肝细胞癌(Hepatocellular carcinoma
HCC)是常见的恶性肿瘤之一
治疗手段有限。随着肝癌发生发展过程中关键基因和信号通路认识的深入
一些高选择性、低毒性的靶向药物不断问世
为晚期肝癌的治疗带来了多种选择。本文综述了肝细胞癌靶向治疗的代表性药物和潜在靶点的研究进展。
Hepatocellular carcinoma (HCC) is one of the most common malignancies
and its treatment is limited. With the understanding of key genes and signaling pathways in the occurrence and development of HCC
targeted drugs with high selectivity and low toxicity have been developed continuously
bringing a variety of options for the treatment of advanced HCC. In this article
the research progress on representative drugs of targeted therapy and potential therapeutic targets for HCC are reviewed.
Yang JD , Hainaut P , Gores GJ , et al . A global view of hepatocellular carcinoma: trends, risk, prevention and management . Nat Rev Gastroenterol Hepatol , 2019 ; 16 ( 10 ): 589 - 604 . doi: 10.1038/s41575-019-0186-y 1001-9294-36-1-57/s41575-019-0186-y . DOI: 10.1038/s41575-019-0186-y http://doi.org/10.1038/s41575-019-0186-y https://www.ncbi.nlm.nih.gov/pubmed/31439937 https://www.ncbi.nlm.nih.gov/pubmed/31439937
Wang H , Lu Z , Zhao X . Tumorigenesis, diagnosis, and therapeutic potential of exosomes in liver cancer . J Hematol Oncol 2019 ; 12 ( 1 ): 133 . doi: 10.1186/s13045-019-0806-6 1001-9294-36-1-57/s13045-019-0806-6 . DOI: 10.1186/s13045-019-0806-6 http://doi.org/10.1186/s13045-019-0806-6 https://www.ncbi.nlm.nih.gov/pubmed/31815633 https://www.ncbi.nlm.nih.gov/pubmed/31815633
Llovet JM , Montal R , Sia D , et al . Molecular therapies and precision medicine for hepatocellular carcinoma . Nat Rev Clin Oncol 2018 ; 15 ( 10 ): 599 - 616 . doi: 10.1038/s41571-018-0073-4 1001-9294-36-1-57/s41571-018-0073-4 . DOI: 10.1038/s41571-018-0073-4 http://doi.org/10.1038/s41571-018-0073-4 https://www.ncbi.nlm.nih.gov/pubmed/30061739 https://www.ncbi.nlm.nih.gov/pubmed/30061739
Couri T , Pillai A . Goals and targets for personalized therapy for HCC . Hepatol Int 2019 ; 13 ( 2 ): 125 - 37 . doi: 10.1007/s12072-018-9919-1 1001-9294-36-1-57/s12072-018-9919-1 . DOI: 10.1007/s12072-018-9919-1 http://doi.org/10.1007/s12072-018-9919-1 https://www.ncbi.nlm.nih.gov/pubmed/30600478 https://www.ncbi.nlm.nih.gov/pubmed/30600478
Pinter M , Peck-Radosavljevic M . Review article: systemic treatment of hepatocellular carcinoma . Aliment Pharmacol Ther 2018 ; 48 ( 6 ): 598 - 609 . doi: 10.1111/apt.14913 1001-9294-36-1-57/apt.14913 . DOI: 10.1111/apt.14913 http://doi.org/10.1111/apt.14913 https://www.ncbi.nlm.nih.gov/pubmed/30039640 https://www.ncbi.nlm.nih.gov/pubmed/30039640
Li M , Su Y , Zhang F , et al . A dual-targeting reconstituted high density lipoprotein leveraging the synergy of sorafenib and antimiRNA21 for enhanced hepatocellular carcinoma therapy . Acta Biomater 2018 ; 75 : 413 - 26 . doi: 10.1016/j.actbio.2018.05.049 1001-9294-36-1-57/j.actbio.2018.05.049 . DOI: 10.1016/j.actbio.2018.05.049 http://doi.org/10.1016/j.actbio.2018.05.049 https://www.ncbi.nlm.nih.gov/pubmed/29859368 https://www.ncbi.nlm.nih.gov/pubmed/29859368
Matsuki M , Hoshi T , Yamamoto Y , et al . Lenvatinib inhibits angiogenesis and tumor fibroblast growth factor signaling pathways in human hepatocellular carcinoma models . Cancer Med 2018 ; 7 ( 6 ): 2641 - 53 . doi: 10.1002/cam4.1517 1001-9294-36-1-57/cam4.1517 . https://www.ncbi.nlm.nih.gov/pubmed/29733511 https://www.ncbi.nlm.nih.gov/pubmed/29733511
Hoshi T , Watanabe MS , Watanabe H , et al . Lenvatinib induces death of human hepatocellular carcinoma cells harboring an activated FGF signaling pathway through inhibition of FGFR-MAPK cascades . Biochem Biophys Res Commun 2019 ; 513 ( 1 ): 1 - 7 . doi: 10.1016/j.bbrc.2019.02.015 1001-9294-36-1-57/j.bbrc.2019.02.015 . DOI: 10.1016/j.bbrc.2019.02.015 http://doi.org/10.1016/j.bbrc.2019.02.015 https://www.ncbi.nlm.nih.gov/pubmed/30944079 https://www.ncbi.nlm.nih.gov/pubmed/30944079
Kudo M , Finn RS , Qin S , et al . Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial . Lancet 2018 ; 391 ( 10126 ): 1163 - 73 . doi: 10.1016/S0140-6736(18)30207-1 1001-9294-36-1-57/S0140-6736(18)30207-1 . https://www.ncbi.nlm.nih.gov/pubmed/29433850 https://www.ncbi.nlm.nih.gov/pubmed/29433850
Kobayashi M , Kudo M , Izumi N , et al . Cost-effectiveness analysis of lenvatinib treatment for patients with unresectable hepatocellular carcinoma (uHCC) compared with sorafenib in Japan . J Gastroenterol 2019 ; 54 ( 6 ): 558 - 70 . doi: 10.1007/s00535-019-01554-0 1001-9294-36-1-57/s00535-019-01554-0 . DOI: 10.1007/s00535-019-01554-0 http://doi.org/10.1007/s00535-019-01554-0 https://www.ncbi.nlm.nih.gov/pubmed/30788569 https://www.ncbi.nlm.nih.gov/pubmed/30788569
Bruix J , Qin S , Merle P , et al . Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial . Lancet 2017 ; 389 ( 10064 ): 56 - 66 . doi: 10.1016/S0140-6736(16)32453-9 1001-9294-36-1-57/S0140-6736(16)32453-9 . DOI: 10.1016/S0140-6736(16)32453-9 http://doi.org/10.1016/S0140-6736(16)32453-9 https://www.ncbi.nlm.nih.gov/pubmed/27932229 https://www.ncbi.nlm.nih.gov/pubmed/27932229
Ogasawara S , Ooka Y , Itokawa N , et al . Sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a multicenter retrospective study in Japan . Invest New Drugs 2020 ; 38 ( 1 ): 172 - 80 . doi: 10.1007/s10637-019-00801-8 1001-9294-36-1-57/s10637-019-00801-8 . DOI: 10.1007/s10637-019-00801-8 http://doi.org/10.1007/s10637-019-00801-8 https://www.ncbi.nlm.nih.gov/pubmed/31172442 https://www.ncbi.nlm.nih.gov/pubmed/31172442
Yoo C , Park JW , Kim YJ , et al . Multicenter retrospective analysis of the safety and efficacy of regorafenib after progression on sorafenib in Korean patients with hepatocellular carcinoma . Invest New Drugs 2019 ; 37 ( 3 ): 567 - 72 . doi: 10.1007/s10637-018-0707-5 1001-9294-36-1-57/s10637-018-0707-5 . DOI: 10.1007/s10637-018-0707-5 http://doi.org/10.1007/s10637-018-0707-5 https://www.ncbi.nlm.nih.gov/pubmed/30523474 https://www.ncbi.nlm.nih.gov/pubmed/30523474
Ogasawara S , Chiba T , Ooka Y , et al . Characteristics of patients with sorafenib-treated advanced hepatocellular carcinoma eligible for second-line treatment . Invest New Drugs 2018 ; 36 ( 2 ): 332 - 9 . doi: 10.1007/s10637-017-0507-3 1001-9294-36-1-57/s10637-017-0507-3 . DOI: 10.1007/s10637-017-0507-3 http://doi.org/10.1007/s10637-017-0507-3 https://www.ncbi.nlm.nih.gov/pubmed/28891038 https://www.ncbi.nlm.nih.gov/pubmed/28891038
Finn RS , Merle P , Granito A , et al . Outcomes of sequential treatment with sorafenib followed by regorafenib for HCC: Additional analyses from the phase III RESORCE trial . J Hepatol 2018 ; 69 ( 2 ): 353 - 8 . doi: 10.1016/j.jhep.2018.04.010 1001-9294-36-1-57/j.jhep.2018.04.010 . DOI: 10.1016/j.jhep.2018.04.010 http://doi.org/10.1016/j.jhep.2018.04.010 https://www.ncbi.nlm.nih.gov/pubmed/29704513 https://www.ncbi.nlm.nih.gov/pubmed/29704513
Yang C , Qin S . Apatinib targets both tumor and endothelial cells in hepatocellular carcinoma . Cancer Med 2018 ; 7 ( 9 ): 4570 - 83 . doi: 10.1002/cam4.1664 1001-9294-36-1-57/cam4.1664 . DOI: 10.1002/cam4.1664 http://doi.org/10.1002/cam4.1664 https://www.ncbi.nlm.nih.gov/pubmed/30109780 https://www.ncbi.nlm.nih.gov/pubmed/30109780
Zhang H , Cao Y , Chen Y , et al . Apatinib promotes apoptosis of the SMMC-7721 hepatocellular carcinoma cell line via the PI3K/Akt pathway . Oncol Lett 2018 ; 15 ( 4 ): 5739 - 43 . doi: 10.3892/ol.2018.8031 1001-9294-36-1-57/ol.2018.8031 . DOI: 10.3892/ol.2018.8031 http://doi.org/10.3892/ol.2018.8031 https://www.ncbi.nlm.nih.gov/pubmed/29552208 https://www.ncbi.nlm.nih.gov/pubmed/29552208
Yu WC , Zhang KZ , Chen SG , et al . Efficacy and Safety of apatinib in patients with intermediate/advanced hepatocellular carcinoma: A prospective observation study . Medicine (Baltimore) 2018 ; 97 ( 3 ): e9704 . doi: 10.1097/MD.0000000000009704 1001-9294-36-1-57/MD.0000000000009704 .
Xue JM , Astère M , Zhong MX , et al . Efficacy and safety of apatinib treatment for gastric cancer, hepatocellular carcinoma and non-small cell lung cancer: a meta-analysis . Onco Targets Ther 2018 ; 11 : 6119 - 28 . doi: 10.2147/OTT.S172717 1001-9294-36-1-57/OTT.S172717 . DOI: 10.2147/OTT.S172717 http://doi.org/10.2147/OTT.S172717 https://www.ncbi.nlm.nih.gov/pubmed/30288047 https://www.ncbi.nlm.nih.gov/pubmed/30288047
Wang Y , Gou Q , Xu R , et al . Efficacy and safety of sorafenib versus apatinib in the treatment of intermediate and advanced hepatocellular carcinoma: a comparative retrospective study . Onco Targets Ther 2018 ; 11 : 3407 - 13 . doi: 10.2147/OTT.S161023 1001-9294-36-1-57/OTT.S161023 .
Wang Y , Tang Z . A novel long-sustaining system of apatinib for long-term inhibition of the proliferation of hepatocellular carcinoma cells . Onco Targets Ther 2018 ; 11 : 8529 - 41 . doi: 10.2147/OTT.S188209 1001-9294-36-1-57/OTT.S188209 . DOI: 10.2147/OTT.S188209 http://doi.org/10.2147/OTT.S188209 https://www.ncbi.nlm.nih.gov/pubmed/30555243 https://www.ncbi.nlm.nih.gov/pubmed/30555243
Liu Z , Wang C , Wu G , et al . MRI analysis of hydrogel-loaded apatinib for local therapy of hepatocellular carcinoma model in nude mice . Biochem Biophys Res Commun 2019 ; 509 ( 2 ): 529 - 34 . doi: 10.1016/j.bbrc.2018.12.120 1001-9294-36-1-57/j.bbrc.2018.12.120 . DOI: 10.1016/j.bbrc.2018.12.120 http://doi.org/10.1016/j.bbrc.2018.12.120 https://www.ncbi.nlm.nih.gov/pubmed/30598262 https://www.ncbi.nlm.nih.gov/pubmed/30598262
Zhu Y , Feng B , Mei L , et al . Clinical efficacy of TACE combined with Apatinib in the treatment of advanced hepatocellular carcinoma . J BUON 2019 ; 24 ( 2 ): 608 - 14 . doi: 10.1109/5.771073 1001-9294-36-1-57/5.771073 . https://www.ncbi.nlm.nih.gov/pubmed/31128013 https://www.ncbi.nlm.nih.gov/pubmed/31128013
Liu C , Xing W , Si T , et al . Efficacy and safety of apatinib combined with transarterial chemoembolization for hepatocellular carcinoma with portal venous tumor thrombus: a retrospective study . Oncotarget 2017 ; 8 ( 59 ): 100734 - 45 . doi: 10.18632/oncotarget.20140 1001-9294-36-1-57/oncotarget.20140 . https://www.ncbi.nlm.nih.gov/pubmed/29246017 https://www.ncbi.nlm.nih.gov/pubmed/29246017
Lu W , Jin XL , Yang C , et al . Comparison of efficacy between TACE combined with apatinib and TACE alone in the treatment of intermediate and advanced hepatocellular carcinoma: A single-center randomized controlled trial . Cancer Biol Ther 2017 ; 18 ( 6 ): 433 - 8 . doi: 10.1080/15384047.2017.1323589 1001-9294-36-1-57/15384047.2017.1323589 . DOI: 10.1080/15384047.2017.1323589 http://doi.org/10.1080/15384047.2017.1323589 https://www.ncbi.nlm.nih.gov/pubmed/28548587 https://www.ncbi.nlm.nih.gov/pubmed/28548587
Zhu AX , Finn RS , Mulcahy M , et al . A phase II and biomarker study of ramucirumab, a human monoclonal antibody targeting the VEGF receptor-2, as first-line monotherapy in patients with advanced hepatocellular cancer . Clin Cancer Res 2013 ; 19 ( 23 ): 6614 - 23 . doi: 10.1158/1078-0432.CCR-13-1442 1001-9294-36-1-57/1078-0432.CCR-13-1442 . DOI: 10.1158/1078-0432.CCR-13-1442 http://doi.org/10.1158/1078-0432.CCR-13-1442 https://www.ncbi.nlm.nih.gov/pubmed/24088738 https://www.ncbi.nlm.nih.gov/pubmed/24088738
Chau I , Peck-Radosavljevic M , Borg C , et al . Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib: Patient-focused outcome results from the randomised phase III REACH study . Eur J Cancer 2017 ; 81 : 17 - 25 . doi: 10.1016/j.ejca.2017.05.001 1001-9294-36-1-57/j.ejca.2017.05.001 . DOI: 10.1016/j.ejca.2017.05.001 http://doi.org/10.1016/j.ejca.2017.05.001 https://www.ncbi.nlm.nih.gov/pubmed/28591675 https://www.ncbi.nlm.nih.gov/pubmed/28591675
Zhu AX , Kang YK , Yen CJ , et al . Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial . Lancet Oncol 2019 ; 20 ( 2 ): 282 - 96 . doi: 10.1016/S1470-2045(18)30937-9 1001-9294-36-1-57/S1470-2045(18)30937-9 . DOI: 10.1016/S1470-2045(18)30937-9 http://doi.org/10.1016/S1470-2045(18)30937-9 https://www.ncbi.nlm.nih.gov/pubmed/30665869 https://www.ncbi.nlm.nih.gov/pubmed/30665869
Siegel AB , Cohen EI , Ocean A , et al . Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma . J Clin Oncol 2008 ; 26 ( 18 ): 2992 - 8 . doi: 10.1200/JCO.2007.15.9947 1001-9294-36-1-57/JCO.2007.15.9947 . DOI: 10.1200/JCO.2007.15.9947 http://doi.org/10.1200/JCO.2007.15.9947 https://www.ncbi.nlm.nih.gov/pubmed/18565886 https://www.ncbi.nlm.nih.gov/pubmed/18565886
Hubbard JM , Mahoney MR , Loui WS , et al . Phase I/II Randomized Trial of Sorafenib and Bevacizumab as First-Line Therapy in Patients with Locally Advanced or Metastatic Hepatocellular Carcinoma: North Central Cancer Treatment Group Trial N0745 (Alliance) . Target Oncol 2017 ; 12 ( 2 ): 201 - 9 . doi: 10.1007/s11523-016-0467-0 1001-9294-36-1-57/s11523-016-0467-0 . DOI: 10.1007/s11523-016-0467-0 http://doi.org/10.1007/s11523-016-0467-0 https://www.ncbi.nlm.nih.gov/pubmed/27943153 https://www.ncbi.nlm.nih.gov/pubmed/27943153
Thomas MB , Garrett-Mayer E , Anis M , et al . A randomized phase II open-label multi-institution study of the combination of bevacizumab and erlotinib compared to sorafenib in the first-line treatment of patients with advanced hepatocellular carcinoma . Oncology 2018 ; 94 ( 6 ): 329 - 39 . doi: 10.1159/000485384 1001-9294-36-1-57/000485384 . DOI: 10.1159/000485384 http://doi.org/10.1159/000485384 https://www.ncbi.nlm.nih.gov/pubmed/29719302 https://www.ncbi.nlm.nih.gov/pubmed/29719302
Cheng AL , Kang YK , Lin DY , et al . Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial . J Clin Oncol 2013 ; 31 ( 32 ): 4067 - 75 . doi: 10.1200/JCO.2012.45.8372 1001-9294-36-1-57/JCO.2012.45.8372 . DOI: 10.1200/JCO.2012.45.8372 http://doi.org/10.1200/JCO.2012.45.8372 https://www.ncbi.nlm.nih.gov/pubmed/24081937 https://www.ncbi.nlm.nih.gov/pubmed/24081937
Pokuri VK , Tomaszewski GM , Ait-Oudhia S , et al . Efficacy, Safety, and Potential Biomarkers of Sunitinib and Transarterial Chemoembolization (TACE) Combination in Advanced Hepatocellular Carcinoma (HCC): Phase II Trial . Am J Clin Oncol 2018 ; 41 ( 4 ): 332 - 8 . doi: 10.1097/COC.0000000000000286 1001-9294-36-1-57/COC.0000000000000286 . DOI: 10.1097/COC.0000000000000286 http://doi.org/10.1097/COC.0000000000000286 https://www.ncbi.nlm.nih.gov/pubmed/27014931 https://www.ncbi.nlm.nih.gov/pubmed/27014931
Johnson PJ , Qin S , Park JW , et al . Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: results from the randomized phase III BRISK-FL study . J Clin Oncol 2013 ; 31 ( 28 ): 3517 - 24 . doi: 10.1200/JCO.2012.48.4410 1001-9294-36-1-57/JCO.2012.48.4410 . DOI: 10.1200/JCO.2012.48.4410 http://doi.org/10.1200/JCO.2012.48.4410 https://www.ncbi.nlm.nih.gov/pubmed/23980084 https://www.ncbi.nlm.nih.gov/pubmed/23980084
Llovet JM , Decaens T , Raoul JL , et al . Brivanib in patients with advanced hepatocellular carcinoma who were intolerant to sorafenib or for whom sorafenib failed: results from the randomized phase III BRISK-PS study . J Clin Oncol 2013 ; 31 ( 28 ): 3509 - 16 . doi: 10.1200/JCO.2012.47.3009 1001-9294-36-1-57/JCO.2012.47.3009 . DOI: 10.1200/JCO.2012.47.3009 http://doi.org/10.1200/JCO.2012.47.3009 https://www.ncbi.nlm.nih.gov/pubmed/23980090 https://www.ncbi.nlm.nih.gov/pubmed/23980090
Qu Z , Jiang C , Wu J , et al . Lenalidomide induces apoptosis and inhibits angiogenesis via caspase-3 and VEGF in hepatocellular carcinoma cells . Mol Med Rep 2016 ; 14 ( 5 ): 4781 - 6 . doi: 10.3892/mmr.2016.5797. Epub 2016 Oct 5 1001-9294-36-1-57/mmr.2016.5797. Epub 2016 Oct 5 . DOI: 10.3892/mmr.2016.5797 http://doi.org/10.3892/mmr.2016.5797 https://www.ncbi.nlm.nih.gov/pubmed/27748917 https://www.ncbi.nlm.nih.gov/pubmed/27748917
Maria de Souza C , Fonseca de Carvalho L , da Silva Vieira T , et al . Thalidomide attenuates mammary cancer associated-inflammation, angiogenesis and tumor growth in mice . Biomed Pharmacother 2012 ; 66 ( 7 ): 491 - 8 . doi: 10.1016/j.biopha.2012.04.005 1001-9294-36-1-57/j.biopha.2012.04.005 . DOI: 10.1016/j.biopha.2012.04.005 http://doi.org/10.1016/j.biopha.2012.04.005 https://www.ncbi.nlm.nih.gov/pubmed/22705333 https://www.ncbi.nlm.nih.gov/pubmed/22705333
Shao YY , Chen BB , Ou DL , et al . Lenalidomide as second-line therapy for advanced hepatocellular carcinoma: exploration of biomarkers for treatment efficacy . Aliment Pharmacol Ther 2017 ; 46 ( 8 ): 722 - 30 . doi: 10.1111/apt.14270 1001-9294-36-1-57/apt.14270 . DOI: 10.1111/apt.14270 http://doi.org/10.1111/apt.14270 https://www.ncbi.nlm.nih.gov/pubmed/28815645 https://www.ncbi.nlm.nih.gov/pubmed/28815645
Ye Q , Qin S , Liu Y , et al . Inhibitory effect of endostar on specific angiogenesis induced by human hepatocellular carcinoma . Gastroenterol Res Pract 2015 ; 2015 : 957574 . doi: 10.1155/2015/957574 1001-9294-36-1-57/2015/957574 . DOI: 10.1155/2015/957574 http://doi.org/10.1155/2015/957574 https://www.ncbi.nlm.nih.gov/pubmed/25983751 https://www.ncbi.nlm.nih.gov/pubmed/25983751
Zhu AX , Ancukiewicz M , Supko JG , et al . Efficacy, safety, pharmacokinetics, and biomarkers of cediranib monotherapy in advanced hepatocellular carcinoma: a phase II study . Clin Cancer Res 2013 ; 19 ( 6 ): 1557 - 66 . doi: 10.1158/1078-0432.CCR-12-3041 1001-9294-36-1-57/1078-0432.CCR-12-3041 . DOI: 10.1158/1078-0432.CCR-12-3041 http://doi.org/10.1158/1078-0432.CCR-12-3041 https://www.ncbi.nlm.nih.gov/pubmed/23362324 https://www.ncbi.nlm.nih.gov/pubmed/23362324
Kang YK , Yau T , Park JW , et al . Randomized phase II study of axitinib versus placebo plus best supportive care in second-line treatment of advanced hepatocellular carcinoma . Ann Oncol 2015 ; 26 ( 12 ): 2457 - 63 . doi: 10.1093/annonc/mdv388 1001-9294-36-1-57/annonc/mdv388 . DOI: 10.1093/annonc/mdv388 http://doi.org/10.1093/annonc/mdv388 https://www.ncbi.nlm.nih.gov/pubmed/26386123 https://www.ncbi.nlm.nih.gov/pubmed/26386123
Cainap C , Qin S , Huang WT , et al . Linifanib versus Sorafenib in patients with advanced hepatocellular carcinoma: results of a randomized phase III trial . J Clin Oncol 2015 ; 33 ( 2 ): 172 - 9 . doi: 10.1200/JCO.2013.54.3298 1001-9294-36-1-57/JCO.2013.54.3298 . DOI: 10.1200/JCO.2013.54.3298 http://doi.org/10.1200/JCO.2013.54.3298 https://www.ncbi.nlm.nih.gov/pubmed/25488963 https://www.ncbi.nlm.nih.gov/pubmed/25488963
Chen YJ , Chi CW , Su WC , et al . Lapatinib induces autophagic cell death and inhibits growth of human hepatocellular carcinoma . Oncotarget 2014 ; 5 ( 13 ): 4845 - 54 . doi: 10.18632/oncotarget.2045 1001-9294-36-1-57/oncotarget.2045 . DOI: 10.18632/oncotarget.2045 http://doi.org/10.18632/oncotarget.2045 https://www.ncbi.nlm.nih.gov/pubmed/24947784 https://www.ncbi.nlm.nih.gov/pubmed/24947784
Chen JY , Huang WC , Wei CT , et al . The C-terminus of hepatitis B virus-encoded X protein is required for lapatinib sensitivity in hepatocellular carcinoma cells . Anticancer Res 2019 ; 39 ( 2 ): 721 - 6 . doi: 10.21873/anticanres.13168 1001-9294-36-1-57/anticanres.13168 . DOI: 10.21873/anticanres.13168 http://doi.org/10.21873/anticanres.13168 https://www.ncbi.nlm.nih.gov/pubmed/30711950 https://www.ncbi.nlm.nih.gov/pubmed/30711950
Huether A , Höpfner M , Baradari V , et al . EGFR blockade by cetuximab alone or as combination therapy for growth control of hepatocellular cancer . Biochem Pharmacol 2005 ; 70 ( 11 ): 1568 - 78 . doi: 10.1016/j.bcp.2005.09.007 1001-9294-36-1-57/j.bcp.2005.09.007 . DOI: 10.1016/j.bcp.2005.09.007 http://doi.org/10.1016/j.bcp.2005.09.007 https://www.ncbi.nlm.nih.gov/pubmed/16226226 https://www.ncbi.nlm.nih.gov/pubmed/16226226
Geng J , Li X , Lang X , et al . Combination of cetuximab and rapamycin enhances the therapeutic efficacy in hepatocellular carcinoma . Technol Cancer Res Treat 2014 ; 13 ( 4 ): 377 - 85 . doi: 10.7785/tcrt.2012.500389 1001-9294-36-1-57/tcrt.2012.500389 . DOI: 10.7785/tcrt.2012.500389 http://doi.org/10.7785/tcrt.2012.500389 https://www.ncbi.nlm.nih.gov/pubmed/24325131 https://www.ncbi.nlm.nih.gov/pubmed/24325131
Zhang J , Zong Y , Xu GZ , et al . Erlotinib for advanced hepatocellular carcinoma. A systematic review of phase II/III clinical trials . Saudi Med J 2016 ; 37 ( 11 ): 1184 - 90 . doi: 10.15537/smj.2016.11.16267 1001-9294-36-1-57/smj.2016.11.16267 . DOI: 10.15537/smj.2016.11.16267 http://doi.org/10.15537/smj.2016.11.16267 https://www.ncbi.nlm.nih.gov/pubmed/27761555 https://www.ncbi.nlm.nih.gov/pubmed/27761555
Zhu AX , Rosmorduc O , Evans TR , et al . SEARCH: a phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma . J Clin Oncol 2015 ; 33 ( 6 ): 559 - 66 . doi: 10.1200/JCO.2013.53.7746 1001-9294-36-1-57/JCO.2013.53.7746 . DOI: 10.1200/JCO.2013.53.7746 http://doi.org/10.1200/JCO.2013.53.7746 https://www.ncbi.nlm.nih.gov/pubmed/25547503 https://www.ncbi.nlm.nih.gov/pubmed/25547503
He L , Deng H , Lei J , et al . Efficacy of bevacizumab combined with erlotinib for advanced hepatocellular carcinoma: a single-arm meta-analysis based on prospective studies . BMC Cancer 2019 ; 19 ( 1 ): 276 . doi: 10.1186/s12885-019-5487-6 1001-9294-36-1-57/s12885-019-5487-6 . DOI: 10.1186/s12885-019-5487-6 http://doi.org/10.1186/s12885-019-5487-6 https://www.ncbi.nlm.nih.gov/pubmed/30922256 https://www.ncbi.nlm.nih.gov/pubmed/30922256
Yanik EL , Chinnakotla S , Gustafson SK , et al . Effects of maintenance immunosuppression with sirolimus after liver transplant for hepatocellular carcinoma . Liver Transpl 2016 ; 22 ( 5 ): 627 - 34 . doi: 10.1002/lt.24395 1001-9294-36-1-57/lt.24395 . DOI: 10.1002/lt.24395 http://doi.org/10.1002/lt.24395 https://www.ncbi.nlm.nih.gov/pubmed/26784951 https://www.ncbi.nlm.nih.gov/pubmed/26784951
Geissler EK , Schnitzbauer AA , Zülke C , et al . Sirolimus use in liver transplant recipients with hepatocellular carcinoma: a randomized, multicenter, open-label phase 3 trial . Transplantation 2016 ; 100 ( 1 ): 116 - 25 . doi: 10.1097/TP.0000000000000965 1001-9294-36-1-57/TP.0000000000000965 . DOI: 10.1097/TP.0000000000000965 http://doi.org/10.1097/TP.0000000000000965 https://www.ncbi.nlm.nih.gov/pubmed/26555945 https://www.ncbi.nlm.nih.gov/pubmed/26555945
Zhu AX , Kudo M , Assenat E , et al . Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial . JAMA 2014 ; 312 ( 1 ): 57 - 67 . doi: 10.1001/jama.2014.7189 1001-9294-36-1-57/jama.2014.7189 . DOI: 10.1001/jama.2014.7189 http://doi.org/10.1001/jama.2014.7189 https://www.ncbi.nlm.nih.gov/pubmed/25058218 https://www.ncbi.nlm.nih.gov/pubmed/25058218
Koeberle D , Dufour JF , Demeter G , et al . Sorafenib with or without everolimus in patients with advanced hepatocellular carcinoma (HCC): a randomized multicenter, multinational phase II trial (SAKK 77/08 and SASL 29) . Ann Oncol 2016 ; 27 ( 5 ): 856 - 61 . doi: 10.1093/annonc/mdw054 1001-9294-36-1-57/annonc/mdw054 . DOI: 10.1093/annonc/mdw054 http://doi.org/10.1093/annonc/mdw054 https://www.ncbi.nlm.nih.gov/pubmed/26884590 https://www.ncbi.nlm.nih.gov/pubmed/26884590
TCC Y , Lencioni R , Sukeepaisarnjaroen W , et al . A phase Ⅰ/Ⅱ multicenter study of single-agent foretinib as first-line therapy in patients with advanced hepatocellular carcinoma . Clin Cancer Res 2017 ; 23 ( 10 ): 2405 - 13 . doi: 10.1158/1078-0432.CCR-16-1789 1001-9294-36-1-57/1078-0432.CCR-16-1789 . DOI: 10.1158/1078-0432.CCR-16-1789 http://doi.org/10.1158/1078-0432.CCR-16-1789 https://www.ncbi.nlm.nih.gov/pubmed/27821605 https://www.ncbi.nlm.nih.gov/pubmed/27821605
Abou-Alfa GK , Meyer T , Cheng AL , et al . Cabozantinib in patients with advanced and progressing hepatocellular carcinoma . N Engl J Med 2018 ; 379 ( 1 ): 54 - 63 . doi: 10.1056/NEJMoa1717002 1001-9294-36-1-57/NEJMoa1717002 . DOI: 10.1056/NEJMoa1717002 http://doi.org/10.1056/NEJMoa1717002 https://www.ncbi.nlm.nih.gov/pubmed/29972759 https://www.ncbi.nlm.nih.gov/pubmed/29972759
Soto-Perez-de-Celis E , Aguiar PN , Cordón ML , et al . Cost-effectiveness of cabozantinib in the second-line treatment of advanced hepatocellular carcinoma . J Natl Compr Canc Netw 2019 ; 17 ( 6 ): 669 - 75 . doi: 10.6004/jnccn.2018.7275 1001-9294-36-1-57/jnccn.2018.7275 . DOI: 10.6004/jnccn.2018.7275 http://doi.org/10.6004/jnccn.2018.7275 https://www.ncbi.nlm.nih.gov/pubmed/31200357 https://www.ncbi.nlm.nih.gov/pubmed/31200357
Ringelhan M , Pfister D , O’Connor T , et al . The immunology of hepatocellular carcinoma . Nat Immunol 2018 ; 19 ( 3 ): 222 - 32 . doi: 10.1038/s41590-018-0044-z 1001-9294-36-1-57/s41590-018-0044-z . DOI: 10.1038/s41590-018-0044-z http://doi.org/10.1038/s41590-018-0044-z https://www.ncbi.nlm.nih.gov/pubmed/29379119 https://www.ncbi.nlm.nih.gov/pubmed/29379119
Facciorusso A , Licinio R , Carr BI , et al . MEK 1/2 inhibitors in the treatment of hepatocellular carcinoma . Expert Rev Gastroenterol Hepatol 2015 ; 9 ( 7 ): 993 - 1003 . doi: 10.1586/17474124.2015.1040763 1001-9294-36-1-57/17474124.2015.1040763 . DOI: 10.1586/17474124.2015.1040763 http://doi.org/10.1586/17474124.2015.1040763 https://www.ncbi.nlm.nih.gov/pubmed/25915713 https://www.ncbi.nlm.nih.gov/pubmed/25915713
Tai WM , Yong WP , Lim C , et al . A phase Ib study of selumetinib (AZD6244, ARRY-142886) in combination with sorafenib in advanced hepatocellular carcinoma (HCC) . Ann Oncol 2018 ; 29 ( 2 ): 526 . doi: 10.1093/annonc/mdx060 1001-9294-36-1-57/annonc/mdx060 . DOI: 10.1093/annonc/mdx060 http://doi.org/10.1093/annonc/mdx060 https://www.ncbi.nlm.nih.gov/pubmed/28368515 https://www.ncbi.nlm.nih.gov/pubmed/28368515
Lim HY , Heo J , Choi HJ , et al . A phase II study of the efficacy and safety of the combination therapy of the MEK inhibitor refametinib (BAY 86-9766) plus sorafenib for Asian patients with unresectable hepatocellular carcinoma . Clin Cancer Res 2014 ; 20 ( 23 ): 5976 - 85 . doi: 10.1158/1078-0432.CCR-13-3445 1001-9294-36-1-57/1078-0432.CCR-13-3445 . DOI: 10.1158/1078-0432.CCR-13-3445 http://doi.org/10.1158/1078-0432.CCR-13-3445 https://www.ncbi.nlm.nih.gov/pubmed/25294897 https://www.ncbi.nlm.nih.gov/pubmed/25294897
Lim HY , Merle P , Weiss KH , et al . Phase II studies with refametinib or refametinib plus sorafenib in patients with RAS-mutated hepatocellular carcinoma . Clin Cancer Res 2018 ; 24 ( 19 ): 4650 - 61 . doi: 10.1158/1078-0432.CCR-17-3588 1001-9294-36-1-57/1078-0432.CCR-17-3588 . DOI: 10.1158/1078-0432.CCR-17-3588 http://doi.org/10.1158/1078-0432.CCR-17-3588 https://www.ncbi.nlm.nih.gov/pubmed/29950351 https://www.ncbi.nlm.nih.gov/pubmed/29950351
Abou-Alfa GK , Capanu M , O’Reilly EM , et al . A phase II study of cixutumumab (IMC-A12, NSC742460) in advanced hepatocellular carcinoma . J Hepatol 2014 ; 60 ( 2 ): 319 - 24 . doi: 10.1016/j.jhep.2013.09.008 1001-9294-36-1-57/j.jhep.2013.09.008 . DOI: 10.1016/j.jhep.2013.09.008 http://doi.org/10.1016/j.jhep.2013.09.008 https://www.ncbi.nlm.nih.gov/pubmed/24045151 https://www.ncbi.nlm.nih.gov/pubmed/24045151
El-Khoueiry AB , O’Donnell R , Semrad TJ , et al . A phase I trial of escalating doses of cixutumumab (IMC-A12) and sorafenib in the treatment of advanced hepatocellular carcinoma . Cancer Chemother Pharmacol 2018 ; 81 ( 5 ): 957 - 63 . doi: 10.1007/s00280-018-3553-4 1001-9294-36-1-57/s00280-018-3553-4 . DOI: 10.1007/s00280-018-3553-4 http://doi.org/10.1007/s00280-018-3553-4 https://www.ncbi.nlm.nih.gov/pubmed/29520435 https://www.ncbi.nlm.nih.gov/pubmed/29520435
Scott LJ . Larotrectinib: First Global Approval . Drugs 2019 ; 79 ( 2 ): 201 - 6 . doi: 10.1007/s40265-018-1044-x 1001-9294-36-1-57/s40265-018-1044-x . DOI: 10.1007/s40265-018-1044-x http://doi.org/10.1007/s40265-018-1044-x https://www.ncbi.nlm.nih.gov/pubmed/30635837 https://www.ncbi.nlm.nih.gov/pubmed/30635837
Liu D , Offin M , Harnicar S , et al . Entrectinib: an orally available, selective tyrosine kinase inhibitor for the treatment of NTRK, ROS1, and ALK fusion-positive solid tumors . Ther Clin Risk Manag 2018 ; 14 : 1247 - 52 . doi: 10.2147/TCRM.S147381 1001-9294-36-1-57/TCRM.S147381 . DOI: 10.2147/TCRM.S147381 http://doi.org/10.2147/TCRM.S147381 https://www.ncbi.nlm.nih.gov/pubmed/30050303 https://www.ncbi.nlm.nih.gov/pubmed/30050303
Doebele RC , Drilon A , Paz-Ares L , et al . Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials . Lancet Oncol 2020 ; 21 ( 2 ): 271 - 82 . doi: 10.1016/S1470-2045(19)30691-6 1001-9294-36-1-57/S1470-2045(19)30691-6 . DOI: 10.1016/S1470-2045(19)30691-6 http://doi.org/10.1016/S1470-2045(19)30691-6 https://www.ncbi.nlm.nih.gov/pubmed/31838007 https://www.ncbi.nlm.nih.gov/pubmed/31838007
Tomás-Loba A , Manieri E , González-Terán B , et al . p38γ is essential for cell cycle progression and liver tumorigenesis . Nature 2019 ; 568 ( 7753 ): 557 - 60 . doi: 10.1038/s41586-019-1112-8 1001-9294-36-1-57/s41586-019-1112-8 . DOI: 10.1038/s41586-019-1112-8 http://doi.org/10.1038/s41586-019-1112-8 https://www.ncbi.nlm.nih.gov/pubmed/30971822 https://www.ncbi.nlm.nih.gov/pubmed/30971822
Chen DT , Pan JH , Chen YH , et al . The mu-opioid receptor is a molecular marker for poor prognosis in hepatocellular carcinoma and represents a potential therapeutic target . Br J Anaesth 2019 ; 122 ( 6 ): e157 - e167 . doi: 10.1016/j.bja.2018.09.030 1001-9294-36-1-57/j.bja.2018.09.030 . DOI: 10.1016/j.bja.2018.09.030 http://doi.org/10.1016/j.bja.2018.09.030 https://www.ncbi.nlm.nih.gov/pubmed/30915986 https://www.ncbi.nlm.nih.gov/pubmed/30915986
Chan KK , Leung CO , Wong CC , et al . Secretory Stanniocalcin 1 promotes metastasis of hepatocellular carcinoma through activation of JNK signaling pathway . Cancer Lett 2017 ; 403 : 330 - 8 . doi: 10.1016/j.canlet.2017.06.034 1001-9294-36-1-57/j.canlet.2017.06.034 . DOI: 10.1016/j.canlet.2017.06.034 http://doi.org/10.1016/j.canlet.2017.06.034 https://www.ncbi.nlm.nih.gov/pubmed/28688970 https://www.ncbi.nlm.nih.gov/pubmed/28688970
Moon H , Cho K , Shin S , et al . High risk of hepatocellular carcinoma development in fibrotic liver: role of the hippo-yap/taz signaling pathway . Int J Mol Sci 2019 ; 20 ( 3 ): 581 . doi: 10.3390/ijms20030581 1001-9294-36-1-57/ijms20030581 .
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