中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 36 Issue 10
Oct.  2020
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Article Contents

Research advances in systemic therapy for hepatocellular carcinoma in the era of precision medicine

DOI: 10.3969/j.issn.1001-5256.2020.10.003
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  • Received Date: 2020-09-14
  • Published Date: 2020-10-20
  • Hepatocellular carcinoma( HCC) is one of the most common malignant tumors in clinical practice and has the features of high incidence rate,poor prognosis,and high mortality rate,and its incidence rate and mortality rate rank among the top malignant tumors in the world. High heterogeneity of HCC affects the evolution and therapeutic response of HCC. Since most HCC patients are in the advanced stage at the time of diagnosis,systemic treatment has become the main treatment option. In recent years,remarkable achievements have been made in molecular targeted therapy and immunotherapy for HCC,and the latest NCCN guidelines for the systemic treatment of HCC show that sorafenib,lenvatinib,and atezolizumab combined with bevacizumab are recommended as the first-line treatment of HCC,and regorafenib,cabozantinib,nivolumab,pembrolizumab,and ramucirumab are the second-line treatment options for HCC. In the era of precision medicine,how to select the optimal individualized systemic treatment regimen is the key problem in the systemic treatment of HCC. This article reviews the advances in the systemic treatment of HCC in the era of precision medicine and discusses the development direction of HCC treatment in the future.

     

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  • [1] YANG SZ,FENG XB,DONG JH. Surgical treatment of liver cancer guided by the concept of precision surgery[J]. J Pre Med,2018,33(3):189-192,196.(in Chinese)杨世忠,冯晓彬,董家鸿.精准外科理念指导下的肝癌外科治疗[J].精准医学杂志,2018,33(3):189-192,196.
    [2] CHEN Z,WANG J. Consideration in the diagnosis and treatment of hepatic cancer based onevidence-based guidelines and precision medicine[J]. Lingnan Mod Clin Surg,2018,18(6):615-617.(in Chinese)陈政,王捷.基于循证指南和精准医学时代背景下肝癌诊疗的思考与总结[J].岭南现代临床外科,2018,18(6):615-617.
    [3] LU SC,GU WQ. Essentials of precision medicine in practice of surgical oncology for hepatobiliary tumors[J]. Chin J Hepatobiliary Surg,2019,25(1):1-4.(in Chinese)卢实春,顾万清.肝胆肿瘤外科治疗精准医学概要[J].中华肝胆外科杂志,2019,25(1):1-4.
    [4] SCHULZE K,NAULT JC,VILLANUEVA A. Genetic profiling of hepatocellular carcinoma using next-generation sequencing[J]. J Hepatol,2016,65(5):1031-1042.
    [5] FORNER A,REIG M,BRUIX J. Hepatocellular carcinoma[J].Lancet,2018,391(10127):1301-1314.
    [6] GAO Q,ZHU H,DONG L,et al. Integrated proteogenomic characterization of HBV-related hepatocellular carcinoma[J]. Cell,2019,179(5):1240.
    [7] European Association for the Study of the Liver. EASL clinical practice guidelines:Management of hepatocellular carcinoma[J]. J Hepatol,2018,69(1):182-236.
    [8] HEIMBACH JK,KULIK LM,FINN RS,et al. AASLD guidelines for the treatment of hepatocellular carcinoma[J]. Hepatology,2018,67(1):358-380.
    [9] LLOVET JM,RICCI S,MAZZAFERRO V,et al. Sorafenib in advanced hepatocellular carcinoma[J]. N Engl J Med,2008,359:378-390.
    [10] SCHULZE K,IMBEAUD S,LETOUZE,et al. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets[J]. Nat Genet,2015,47(5):505-511.
    [11] GYAWALI B,PRASAD V. Health policy:Me-too drugs with limited benefits-the tale of regorafenib for HCC[J]. Nat Rev Clin Oncol,2017,14(11):653-654.
    [12] SAWEY ET,CHANRION M,CAI C,et al. Identification of a therapeutic strategy targeting amplified FGF19 in liver cancer by Oncogenomic screening[J]. Cancer Cell,2011,19(3):347-358.
    [13] VILGRAIN V,PEREIRA H,ASSENAT E,et al. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma(SARAH):An open-label randomised controlled phase 3 trial[J]. Lancet Oncol,2017,18(12):1624-1636.
    [14] CHENG AL,KANG YK,CHEN Z,et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma:A phase III randomised,doubleblind,placebo-controlled trial[J]. Lancet Oncol,2009,10(1):25-34.
    [15] BRUIX J,RAOUL JL,SHERMAN M,et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma:Subanalyses of a phase III trial[J]. J Hepatol,2012,57(4):821-829.
    [16] MARRERO JA,KUDO M,VENOOK AP,et al. Observational registry of sorafenib use in clinical practice across ChildPugh subgroups:The GIDEON study[J]. J Hepatol,2016,65(6):1140-1147.
    [17] 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]. J Hepatol,2018,69(2):353-358.
    [18] 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[J]. Lancet,2018,391(10126):1163-1173.
    [19] 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]. J Clin Oncol,2015,33(2):172-179.
    [20] CHENG AL,KANG YK,LIN DY,et al. Sunitinib versus sorafenib in advanced hepatocellular cancer:Results of a randomized phase III trial[J]. J Clin Oncol,2013,31(32):4067-4075.
    [21] 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[J]. Lancet, 2017, 389(10064):56-66.
    [22] KELLEY RK,VERSLYPE C,COHN AL,et al. Cabozantinib in hepatocellular carcinoma:Results of a phase 2 placebo-controlled randomized discontinuation study[J]. Ann Oncol,2017,28(3):528-534.
    [23] ABOU-ALFA GK,MEYER T,CHENG AL,et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma[J]. N Engl J Med,2018,379(1):54-63.
    [24] HEINRICH S,CASTVEN D,GALLE PR,et al. Translational considerations to improve response and overcome therapy resistance in immunotherapy for hepatocellular carcinoma[J].Cancers(Basel),2020,12(9):e2495.
    [25] SANGRO B,GOMEZ-MARTIN C,de la MATA M,et al. A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C[J]. J Hepatol,2013,59(1):81-88.
    [26] ZHU AX,FINN RS,EDELINE J,et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib(KEYNOTE-224):A non-randomised,open-label phase 2 trial[J]. Lancet Oncol,2018,19(7):940-952.
    [27] EL-KHOUEIRY AB,SANGRO B,YAU T,et al. Nivolumab in patients with advanced hepatocellular carcinoma(CheckMate040):An open-label,non-comparative,phase 1/2 dose escalation and expansion trial[J]. Lancet, 2017, 389(10088):2492-2502.
    [28] FINN RS,RYOO BY,MERLE P,et al. Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240:A randomized,double-blind,phase III trial[J]. J Clin Oncol,2020,38(3):193-202.
    [29] REBOUISSOU S,LA BELLA T,REKIK S,et al. Proliferation markers are associated with MET expression in hepatocellular carcinoma and predict tivantinib sensitivity in vitro[J]. Clin Cancer Res,2017,23(15):4364-4375.
    [30] HU Z,OTT PA,WU CJ. Towards personalized,tumour-specific,therapeutic vaccines for cancer[J]. Nat Rev Immunol,2018,18(3):168-182.
    [31] NEELAPU SS,LOCKE FL,GO WY. CAR T-cell therapy in large B-cell lymphoma[J]. N Engl J Med,2018,378(11):1065.
    [32] NEELAPU SS,TUMMALA S,KEBRIAEI P,et al. Chimeric antigen receptor T-cell therapy-assessment and management of toxicities[J]. Nat Rev Clin Oncol,2018,15(1):47-62.
    [33] PARK R,ESHRAT F,AL-JUMAYLI M,et al. Immuno-oncotherapeutic approaches in advanced hepatocellular carcinoma[J]. Vaccines(Basel),2020,8(3):e447.
    [34] PENG L,BIAN XW,LI DK,et al. Large-scale RNA-Seq transcriptome analysis of 4043 cancers and 548 normal tissue controls across 12 TCGA cancer types[J]. Sci Rep,2015,5:13413.
    [35] FINN RS,QIN S,IKEDA M,et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma[J]. N Engl J Med,2020,382(20):1894-1905.
    [36] FINN RS,IKEDA M,ZHU AX,et al. Phase Ib study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma[J]. J Clin Oncol,2020,38(26):2960-2970.
    [37] KELLEY RK,W OLIVER J,HAZRA S,et al. Cabozantinib in combination with atezolizumab versus sorafenib in treatmentnaive advanced hepatocellular carcinoma:COSMIC-312Phase III study design[J]. Future Oncol,2020,16(21):1525-1536.
    [38] GUARDASCIONE M,TOFFOLI G. Immune checkpoint inhibitors as monotherapy or within a combinatorial strategy in advanced hepatocellular carcinoma[J]. Int J Mol Sci,2020,21(17):e6302.
    [39] FENG GS,HANLEY KL,LIANG Y,et al. Improving the efficacy of liver cancer immunotherapy:The power of combined preclinical and clinical studies[J]. Hepatology,2020.[Online ahead of print]
    [40] ZHU XD,LI KS,SUN HC. Adjuvant therapies after curative treatments for hepatocellular carcincma:Current status and prospects[J]. Genes Dis,2020,7(3):359-369.
    [41] CANALE M,ULIVI P,FOSCHI FG,et al. Clinical and circulating biomarkers of survival and recurrence after radiofrequency ablation in patients with hepatocellular carcinoma[J]. Crit Rev Oncol Hematol,2018,129:44-53.
    [42] ZHU HB,ZENG PH,GAO WH,et al. Discussion on the treatment of hepatocarcinoma with the multi-disciplinary integrated treatment team model combining traditional Chinese medicine and western medicine[J]. Guid J Tradit Chin Med Pharmacol,2019,25(22):21-24,31.(in Chinese)朱洪兵,曾普华,郜文辉,等.中西医联合MDT模式在肝癌治疗中的探讨[J].中医药导报,2019,25(22):21-24,31.
    [43] CHUMA M,UOJIMA H,NUMATA K,et al. Early changes in circulating FGF19 and Ang-2 levels as possible predictive biomarkers of clinical response to lenvatinib therapy in hepatocellular carcinoma[J]. Cancers(Basel),2020,12(2):293.
    [44] LEE JJX,CHAN JJ,CHOO SP. Clinical development of cMET inhibition in hepatocellular carcinoma[J]. Diseases,2015,3(4):306-324.
    [45] RIMASSA L,ABBADESSA G,PERSONENI N,et al. Tumor and circulating biomarkers in patients with second-line hepatocellular carcinoma from the randomized phase II study with tivantinib[J]. Oncotarget,2016,7(45):72622-72633.
    [46] JIANG Y,SUN A,ZHAO Y,et al. Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma[J]. Nature,2019,567(7747):257-261.
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