肝细胞癌的靶向治疗

黄燊; 杨成雷; 张志明

doi:10.3969/j.issn.1001-5256.2019.11.041

肝细胞癌的靶向治疗

DOI: 10.3969/j.issn.1001-5256.2019.11.041

广西医科大学附属肿瘤医院肝胆外科

基金项目:

广西教育厅中青年教师基础能力提升项目(KY2016YB085)；广西医疗卫生适宜技术研究与开发项目(卫生厅S201516)；

详细信息

中图分类号: R735.7
计量
- 文章访问数: 902
- HTML全文浏览量: 45
- PDF下载量: 260
- 被引次数: 0
出版历程
- 收稿日期: 2019-07-05
- 出版日期: 2019-11-20

Research advances in targeted therapy for hepatocellular carcinoma

Department of Hepatobiliary Surgery,The Affiliated Tumor Hospital of Guangxi Medical University

Research funding:

摘要

摘要: 肝细胞癌是常见的恶性肿瘤之一,由于起病隐匿,预后差,缺乏特异性,多数患者确诊时已到了晚期。传统的治疗手段,如手术切除、肝移植、放疗、化疗等治疗作用有限,未能使患者明显受益。近年来,随着科技和医疗水平的整体进步,靶向治疗药物由于在肝细胞癌的治疗方面取得的突破性进展而逐渐进入人们的视野,为晚期肝癌患者带来了新的希望。由于靶向药物有较好的分子选择性,能针对性的杀伤肿瘤细胞,尽可能的保护正常组织而受到广泛关注。现就肝细胞癌的靶向治疗进展作一综述。
- 癌,肝细胞 /
- 分子靶向治疗 /
- 治疗学
Abstract: Hepatocellular carcinoma( HCC) is one of the most common malignant tumors. Due to the insidious onset,poor prognosis,and lack of specificity of HCC,most patients have reached the advanced stage at the time of diagnosis. Conventional treatment methods,such as surgical resection,liver transplantation,radiotherapy,and chemotherapy,have limited therapeutic effects and fail to bring significant benefits to patients. With the improvement of science and technology and medical level in recent years,targeted therapy drugs have gradually entered people's vision due to the breakthroughs in the treatment of HCC and thus bring new hope to patients with advanced HCC. Targeted drugs have attracted wide attention due to good molecular selectivity,targeted killing of tumor cells,and protection of normal tissue. This article reviews the research advances in targeted therapy for HCC.
- carcinoma,hepatocellular /
- molecular targeted therapy /
- therapeutics

HTML全文

参考文献(36)

[1] BRAY F,FERLAY J,SOERJOMATARAM I,et al. Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin,2018,68(6):394-424.

[2] CHOI KJ,BAIK IH,YE SK,et al. Molecular targeted therapy for hepatocellular carcinoma:Present status and future directions[J]. Biol Pharm Bull,2015,38(7):986-991.

[3] CHENG A,KANG Y,CHEN Z,et al. Randomized phaseⅢtrial of sorafenib versus placebo in Asian patients with advanced hepatocellular carcinoma[J]. J Clin Oncol,2008,26(20Suppl):4509.

[4] PALMER DH. Sorafenib in advanced hepatocellular carcinoma[J]. N Engl J Med,2008,359(23):2498; author reply 2498-2499.

[5] SUN B,YANG XZ,XIE F,et al. Effect of sorafenib combined with transcatheter arterial chemoembolization and radiofrequency ablation on the survival of patients with hepatocellular carcinoma[J]. J Clin Hepatol,2019,35(1):104-108.

[6] 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-control ed,phase 3 trial[J]. Lancet,2017,389(10064):56-66.

[7] 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.

[8] SHLOMAI A,LESHNO M,GOLDSTEIN DA. Regorafenib treatment for patients with hepatocellular carcinoma who progressed on sorafenib-A cost-effectiveness analysis[J].PLo S One,2018,13(11):e0207132.

[9] CUI YL. Targeted therapy for hepatocellular carcinoma[J].Chin J Dig Surg,2018,17(5):445-451.(in Chinese)崔云龙．肝癌的靶向治疗[J]．中华消化外科杂志，2018,17(5):445-451.

[10] YAMAMOTO Y,MATSUI 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]. Vasc Cell,2014,6:18.

[11] 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.

[12] KUDO M. Lenvatinib may drastically change the treatment landscape of hepatocellular carcinoma[J]. Liver Cancer,2018,7(1):1-19.

[13] Chen SC,CHAO Y,CHEN MH,et al. Lenvatinib for the treatment of HCC:A single institute experience[J]. J Clin Oncol,2019,37(Suppl 15):e15611.

[14] CHANG QQ,PENG Y,WANG GJ,et al. Clinical research progress of small molecule tyrosine kinase inhibitors against hepatocellular carcinoma[J]. Chin J Clin Pharmacol Ther,2019,24(8):948-956.(in Chinese)常青青，彭英，王广基，等．抗肝癌小分子酪氨酸激酶抑制剂的临床研究进展[J]．中国临床药理学与治疗学，2019,24(8):948-956.

[15] ELISEI R,SCHLUMBERGER MJ,MULLER SP,et al. Cabozantinib in progressive medullary thyroid cancer[J]. J Clin Oncol,2013,31(29):3639-3646.

[16] 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.

[17] KUDO M. Cabozantinib as a second-line agent in advanced hepatocellular carcinoma[J]. Liver Cancer,2018,7(2):123-133.

[18] QIN SK,BAI YX,OUYANG XN,et al. Apatinib for patients with advanced hepatocellular carcinoma:A randomised,open-label,multicentre,phaseⅡclinical trial[J]. Chin Clin Oncol,2017,22(12):1057-1065.(in Chinese)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.

[19] WU J,YIN F,LUO GH,et al. Clinical effect and safety of transarterial chemoembolization combined with apatinib in treatment of advanced primary liver cancer[J]. J Clin Hepatol,2018,34(4):775-778.

[20] 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[J]. Oncology,2018,94(6):329-339.

[21] 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[J]. BMC Cancer,2019,19(1):276.

[22] ZHU AX,PARK JO,RYOO BY,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 Oncol,2015,16(7):859-870.

[23] ZHU AX,KANG YK,YEN CJ,et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased alpha-fetoprotein concentrations(REACH-2):A randomised,double-blind,placebo-controlled,phase 3 trial[J]. Lancet Oncol,2019,20(2):282-296.

[24] 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[J]. Jama,2014,312(1):57-67.

[25] CHOLONGITAS E,ANTONIADIS N,GOULIS I,et al. Trough levels of everolimus are associated with recurrence rates of hepatocellular carcinoma after liver transplantation[J]. Transplant Proc,2019,51(2):450-453.

[26] 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.

[27] QIN SK,REN ZG,MENG ZQ,et al. A randomized multicentered phase II study to evaluate SHR-1210(PD-1 antibody)in subjects with advanced hepatocellular carcinoma(HCC)who failed or intolerable to prior systemic treatment[J]. Ann Oncol,2018,29(8):2.

[28] CONTRATTO M,WU J. Targeted therapy or immunotherapy?Optimal treatment in hepatocellular carcinoma[J]. World J Gastrointest Oncol,2018,10(5):108-114.

[29] 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.

[30] EL-KHOUEIRY AB,MELERO I,YAU TC,et al. Impact of antitumor activity on survival outcomes, and nonconventional benefit,with nivolumab(NIVO)in patients with advanced hepatocellular carcinoma(a HCC):Subanalyses of CheckMate-040[J]. J Clin Oncol,2018,36(4suppl):475.

[31] KUDO M,MATILLA A,SANTORO A,et al. Checkmate-040:Nivolumab(NIVO)in patients(pts)with advanced hepatocellular carcinoma(a HCC)and Child-Pugh B(CPB)status[J]. J Clin Oncol,2019,37(4suppl):327.

[32] 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.

[33] ABOU-ALFA GK,QIN S,RYOO BY,et al. Phase III randomized study of second line ADI-PEG 20 plus best supportive care versus placebo plus best supportive care in patients with advanced hepatocellular carcinoma[J]. Ann Oncol,2018,29(6):1402-1408.

[34] IKEDA M,KOBAYASHI M,TAHARA M,et al. Optimal management of patients with hepatocellular carcinoma treated with lenvatinib[J]. Expert Opin Drug Saf,2018,17(11):1095-1105.

[35] IKEDA M,SUNG MW,KUDO M,et al. A phase 1b trial of lenvatinib(LEN)plus pembrolizumab(PEM)in patients(pts)with unresectable hepatocellular carcinoma(u HCC)[J]. J Clin Oncol,2018,36(15suppl):4076-4076.

[36] IKEDA M,SUNG MW,KUDO M,et al. A phase Ib trial of lenvatinib(LEN)plus pembrolizumab(PEMBRO)in unresectable hepatocellular carcinoma(u HCC):Updated results[R].2019 AACR,CT061/18.

施引文献

资源附件(0)

访问统计