网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
肝细胞肝癌靶向与免疫治疗的现状与进展
作者:申重  徐玉清 
单位:哈尔滨医科大学附属第二医院 肿瘤内科, 黑龙江 哈尔滨 150081
关键词:肝细胞肝癌 靶向治疗 免疫治疗 综述 
分类号:R735.7
出版年·卷·期(页码):2019·38·第九期(1164-1168)
摘要:

肝细胞肝癌是一种全球常见的恶性肿瘤,近年来发病率不断升高。大多数肝细胞肝癌发病隐蔽、恶性程度高、预后差。随着现代医学的进步,肝细胞肝癌的治疗方式已不再局限于传统的治疗手段,如手术、放射治疗、化疗,分子靶向治疗作为一种新兴治疗方式已经成为肝细胞肝癌的重要治疗手段。除了分子靶向治疗以外,近年来免疫疗法在肝细胞肝癌的治疗中也取得了很多成果。本文中作者就近年来肝细胞肝癌靶向及免疫治疗的现状与进展作一简要综述。

参考文献:

[1] SIEGEL R L,MILLER K D,JEMAL A.Cancer statistics,2018[J].Ca A Cancer Journal for Clinicians,2018,60(5):277-300.
[2] MATSUDA T,SAIKA K.Trends in liver cancer mortality rates in Japan,USA,UK,France and Korea based on the WHO mortality database[J].Japanese Journal of Clinical Oncology,2012,42(4):360.
[3] YU S J.A concise review of updated guidelines regarding the management of hepatocellular carcinoma around the world:2010-2016[J].Clinical & Molecular Hepatology,2016,22(1):7-17.
[4] SPRINZL M F,GALLE P R.Current progress in immunotherapy of hepatocellular carcinoma[J].Journal of Hepatology,2017,66(3):482-484.
[5] ROTTE A,JIN J Y,LEMAIRE V.Mechanistic overview of immune checkpoints to support the rational design of their combinations in cancer immunotherapy[J].Annals of Oncology,2018,29(1):71-83.
[6] MOEINI A,CORNELLÀ H,VILLANUEVA A.Emerging signaling pathways in hepatocellular carcinoma[J].Liver Cancer,2012,1(2):83-93.
[7] DHANASEKARAN R,BANDOH S,ROBERTS L R.Molecular pathogenesis of hepatocellular carcinoma and impact of therapeutic advances[J].F1000research,2016,5:879-894.
[8] LLOVET J M,RICCI S,MAZZAFERRO V,et al.Sorafenib in advanced hepatocellular carcinoma[J].New Engl J Med,2008,359(4):378-390.
[9] CHENG A L,KANG Y K,CHEN Z,et al.Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma:a phase Ⅲ randomised,double-blind,placebo-controlled trial[J].Lancet Oncol,2009,10(1):25-34.
[10] YAMAMOTO L,MATSUI J J,MATSUSHIMA T,et al.Lenvatinib,an angiogenesis inhibitor targeting VEGFR/FGFR,shows broad antitumor activity in human tumor xenograft models associated with microvessel density and pericyte coverage[J].Vascular Cell,2014,6(1):18.
[11] SCHLUMBERGER M,TAHARA M, LORI J,et al.Lenvatinib versus placebo in radioiodine-refractory thyroid cancer[J].New England Journal of Medicine,2015,372(7):621-630.
[12] MOTZER R J,HUTSON T E,GLEN H,et al.Lenvatinib,everolimus,and the combination in patients with metastatic renal cell carcinoma:a randomised,phase 2,open-label,multicentre trial.[J].Lancet Oncology,2015,16(15):1473-1482.
[13] IKEDA K,KUDO M,KAWAZOE S,et al.Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma[J].Journal of Gastroenterology,2017,52(4):512-519.
[14] KUDO M,FINN R S,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,2018,391:1163-1173.
[15] CHENG A L,KANG Y K,LIN D Y,et al.Sunitinib versus sorafenib in advanced hepatocellular cancer:results of a randomized phase Ⅲ trial.[J].Journal of Clinical Oncology,2013,31(32):4067-4075.
[16] JOHNSON P J,QIN S,PARK J W,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].Journal of Clinical Oncology,2013,56(6):3517-3524.
[17] CAINAP C,QIN S,HUANG W T,et al.Linifanib versus sorafenib in patients with advanced hepatocellular carcinoma:results of a randomized phase Ⅲ trial[J].Journal of Clinical Oncology,2015,33(2):172-179.
[18] ZHU A X,ROSMORDUC O,EVANS T R J,et al.Search:a phase Ⅲ,randomized,double-blind,placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma[J].Journal of Clinical Oncology,2015,33(6):559-566.
[19] BRUIX J,TAK W,GASBARRINI A,et al.Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma:multicentre,open-label,phase Ⅱ safety study[J].European Journal of Cancer,2013,49(16):3412-3419.
[20] 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,2016,389(10064):56-66.
[21] LLOVET J M,DECAENS T,RAOUL J L,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].Journal of Clinical Oncology,2013,31(28):3509-3516.
[22] ZHU A X,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[J].Journal of the American Medical Association,2014,312(1):57-67.
[23] ZHU A X,PARK J O,RYOO B Y,et al.Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH):a randomised,double-blind,multicentre,phase 3 trial.[J].Lancet Oncology,2015,16(7):859-870.
[24] KELLEY R K,VERSLYPE C,COHN A L,et al.Cabozantinib in hepatocellular carcinoma:results of a phase 2 placebo-controlled randomized discontinuation study[J].Annals of Oncology,2017,28(3):528-534.
[25] ABOUALFA G K,MEYER T,CHENG A L,et al.Cabozantinib in patients with advanced and progressing hepatocellular carcinoma[J].New England Journal of Medicine,2018,379(1):54-63.
[26] ZHU A X,KANG Y K,YEN C J,et al.REACH-2:a randomized,doubleblind,placebo-controlled phase 3 study of ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellularcarcinoma (HCC) and elevated baseline alpha-fetoprotein (AFP) following first-line sorafenib[J].J Clin Oncol,2018,36(suppl):abstr4003.
[27] LI J,ZHAO X,CHEN L,et al.Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies[J].BMC Cancer,2010,10(1):529-536.
[28] 秦叔逵,白玉贤,欧阳学农,等.阿帕替尼一线治疗晚期肝细胞癌的前瞻性、随机、开放、全国多中心Ⅱ期临床试验[J].临床肿瘤学杂志,2017,22(12):1057-1065.
[29] LU W,JIN X L,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[J].Cancer Biology & Therapy,2017,18(6):433-438.
[30] 于俊岩,郭红亮,田向阳,等.甲磺酸阿帕替尼联合经导管动脉化疗栓塞治疗肝细胞肝癌的Ⅱ期临床试验[J].东南大学学报(医学版),2018,37(1):74-77.
[31] ESKANDER R N,LONGORIA T C.Immune checkpoint inhibition:therapeutic implications in epithelial ovarian cancer[J].Recent Patents on Anti-Cancer Drug Discovery,2015,10(2):133-144.
[32] PRIETO J,MELERO I.Immunological landscape and immunotherapy of hepatocellular carcinoma[J].Nature Reviews.Gastroenterology & Hepatology,2015,12(12):681-700.
[33] TANEJA S S.Re:safety,activity,and immune correlates of anti-PD-1 antibody in cancer[J].J Urol,2015,67(4):816-817.
[34] EL-KHOUEIRY A B,SANGRO B,YAU T,et al.Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040):an open-label,non-comparative,phase 1/2 dose escalation and expansion trial[J].Lancet,2017,389(10088):2492-2502.
[35] FLYNN M J,SAYED A A,SHARMA R,et al.Challenges and opportunities in the clinical development of immune checkpoint inhibitors for hepatocellular carcinoma[J].Hepatology,2019,69:2258-2270.
[36] ZHU A X,FINN R S, 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].The Lancet Oncology,2018,19(7):940-952.
[37] WALKER L S K,SANSOM D M.The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses[J].Nature Reviews Immunology,2011,11(12):852-863.
[38] CALABR L,MORRA A,FONSATTI E,et al.Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma:an open-label,single-arm,phase 2 trial[J].The Lancet Oncology,2013,14(11):1104-1111.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 751634 位访问者


 ©《现代医学》编辑部
联系电话:025-83272481;83272479
电子邮件: xdyx@pub.seu.edu.cn

苏ICP备09058541