血管内皮生长因子/血管内皮生长因子受体通路在胆管细胞癌发生发展及治疗中的作用

博伦; 张琼; 王祥旭; 潘伟; 张红梅

doi:10.3969/j.issn.1001-5256.2020.08.041

血管内皮生长因子/血管内皮生长因子受体通路在胆管细胞癌发生发展及治疗中的作用

DOI: 10.3969/j.issn.1001-5256.2020.08.041

空军军医大学西京医院肿瘤科

基金项目:

陕西省重点产业创新链课题(2016KTZDSF-01-05)；国家自然科学基金面上项目(81572699)；

详细信息

中图分类号: R735.8
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出版历程
- 出版日期: 2020-08-20

Role of the VEGF/VEGFR pathways in the development,progression,and treatment of cholangiocellular carcinoma

Department of Clinical Oncology, Xijing Hospital, Air Force Medical University

Research funding:

摘要

摘要:
胆管细胞癌(CCA)是源于胆道上皮的恶性肿瘤,缺乏有效的治疗药物,预后不良。研究表明,CCA的发生发展离不开血管生成,以血管内皮生长因子(VEGF)及其受体VEGFR为代表的多种促血管生成因子,均可调节CCA血管生成,参与CCA发生发展并影响其预后。因此,以VEGF/VEGFR为靶点的抗血管生成药物,包括单克隆抗体、小分子抑制剂等,逐渐成为CCA治疗的研究热点。针对VEGF/VEGFR通路在CCA临床特征及预后中的作用、CCA抗血管生成治疗进展及耐药相关研究进行综述。
- 胆管上皮癌 /
- 血管内皮生长因子类 /
- 血管生成抑制剂 /
- 治疗学
Abstract:
Cholangiocellular carcinoma(CCA) is a malignant tumor derived from the biliary epithelium,with a lack of effective therapeutic drugs and poor prognosis.Studies have shown that the development and progression of CCA are closely associated with angiogenesis,and a variety of angiogenic factors,including vascular endothelial growth factor(VEGF) and its receptor VEGFR,can regulate angiogenesis in CCA,participate in the development and progression of CCA,and affect its prognosis.Therefore,anti-angiogenic drugs targeting VEGF/VEGFR,such as monoclonal antibodies and small-molecule inhibitors,have gradually become research hotspots for the treatment of CCA.This article reviews the role of the VEGF/VEGFR pathways in the clinical features and prognosis of CCA,the advances in anti-angiogenic therapy for CCA,and related studies on drug resistance.
- cholangiocarcinoma /
- vascular endothelial growth factors /
- angiogenesis inhibitors /
- therapeutics

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参考文献(47)

[1] MAHIPAL A,KOMMALAPATI A,TELLA SH,et al. Novel targeted treatment options for advanced cholangiocarcinoma[J]. Expert Opin Investig Drugs,2018,27(9):709-720.

[2] RUZZENENTE A,CONCI S,VALDEGAMBERI A,et al. Role of surgery in the treatment of intrahepatic cholangiocarcinoma[J]. Eur Rev Med Pharmacol Sci, 2015, 19(15):2892-2900.

[3] SHIN HR,OH JK,MASUYER E,et al. Comparison of incidence of intrahepatic and extrahepatic cholangiocarcinoma—focus on East and South-Eastern Asia[J]. Asian Pac J Cancer Prev,2010,11(5):1159-1166.

[4] DOHERTY B,NAMBUDIRI VE,PALMER WC. Update on the diagnosis and treatment of cholangiocarcinoma[J]. Curr Gastroenterol Rep,2017,19(1):2.

[5] RIZVI S,KHAN SA,HALLEMEIER CL,et al. Cholangiocarcinoma-evolving concepts and therapeutic strategies[J]. Nat Rev Clin Oncol,2018,15(2):95-111.

[6] SIMONE V,BRUNETTI O,LUPO L,et al. Targeting angiogenesis in biliary tract cancers:An open option[J]. Int J Mol Sci,2017,18(2):418.

[7] YOSHIKAWA D,OJIMA H,IWASAKI M,et al. Clinicopathological and prognostic significance of EGFR, VEGF, and HER2 expression in cholangiocarcinoma[J]. Br J Cancer,2008,98(2):418-425.

[8] ZHAO R,CHANG Y,LIU Z,et al. Effect of vascular endothelial growth factor-C expression on lymph node metastasis in human cholangiocarcinoma[J]. Oncol Lett,2015,10(2):1011-1015.

[9] SHA M,JEONG S,CHEN XS,et al. Expression of VEGFR-3in intrahepatic cholangiocarcinoma correlates with unfavorable prognosis through lymphangiogenesis[J]. Int J Biol Sci,2018,14(10):1333-1342.

[10] HUANG DW,HUANG M,LIN XS,et al. CD155 expression and its correlation with clinicopathologic characteristics,angiogenesis,and prognosis in human cholangiocarcinoma[J].Onco Targets Ther,2017,10:3817-3825.

[11] PENG T,DENG X,TIAN F,et al. The interaction of LOXL2with GATA6 induces VEGFA expression and angiogenesis in cholangiocarcinoma[J]. Int J Oncol, 2019, 55(3):657-670.

[12] YOU Z,BEI L,CHENG LP,et al. Expression of COX-2 and VEGF-C in cholangiocarcinomas at different clinical and pathological stages[J]. Genet Mol Res, 2015, 14(2):6239-6246.

[13] WILHELM SM,CARTER C,TANG L,et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis[J]. Cancer Res,2004,64(19):7099-7109.

[14] HUETHER A,HPFNER M,BARADARI V,et al. Sorafenib alone or as combination therapy for growth control of cholangiocarcinoma[J]. Biochem Pharmacol, 2007, 73(9):1308-1317.

[15] BLECHACZ BR,SMOOT RL,BRONK SF,et al. Sorafenib inhibits signal transducer and activator of transcription-3 signaling in cholangiocarcinoma cells by activating the phosphatase shatterproof 2[J]. Hepatology,2009,50(6):1861-1870.

[16] ZHENG Y,ZHANG J,YE B. miR-138 mediates sorafenibinduced cell survival and is associated with poor prognosis in cholangiocarcinoma cells[J]. Clin Exp Pharmacol Physiol,2020,47(3):459-465.

[17] SUGIYAMA H,ONUKI K,ISHIGE K,et al. Potent in vitro and in vivo antitumor activity of sorafenib against human intrahepatic cholangiocarcinoma cells[J]. J Gastroenterol,2011,46(6):779-789.

[18] TIAN S,QUAN H,XIE C,et al. YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo[J].Cancer Sci,2011,102(7):1374-1380.

[19] CHEN P,IRUELA AL,LOU L,et al. VEGFR inhibitor YN968D1xenograft dose response studies against human colon cancer Ls174t and HT29[J]. Proc Amer Assoc Cancer Res,2006,47(9):1764-1769.

[20] HUANG M,HUANG B,LI G,et al. Apatinib affect VEGF-mediated cell proliferation,migration,invasion via blocking VEGFR2/RAF/MEK/ERK and PI3K/AKT pathways in cholangiocarcinoma cell[J]. BMC Gastroenterol,2018,18(1):169.

[21] PENG H,ZHANG Q,LI J,et al. Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma[J]. Oncotarget,2016,7(13):17220-17229.

[22] ZHANG QS,ZENG J,CHEN Z. Advances in the clinical studies on targeted therapy for advanced renal cell carcinoma[J].J Contemp Urologic Reproduct Oncol,2017,9(3):185-189,192.(in Chinese)张庆松，曾进，陈忠．晚期肾细胞癌靶向治疗的临床研究进展[J]．现代泌尿生殖肿瘤杂志，2017,9(3):185-189,192.

[23] TAKAHASHI H,OJIMA H,SHIMIZU H,et al. Axitinib(AG-013736),an oral specific VEGFR TKI,shows potential therapeutic utility against cholangiocarcinoma[J]. Jpn J Clin Oncol,2014,44(6):570-578.

[24] WEN L,ZHANG HM,XU L. Application of bevacizumab in treatment of colorectal cancer[J]. China Cancer,2016,25(7):534-541.(in Chinese)文磊，张红梅，徐立．贝伐珠单抗在结直肠癌治疗中的应用[J]．中国肿瘤，2016,25(7):534-541.

[25] LUBNER SJ,MAHONEY MR,KOLESAR JL,et al. Report of a multicenter phase II trial testing a combination of biweekly bevacizumab and daily erlotinib in patients with unresectable biliary cancer:A phase II Consortium study[J]. J Clin Oncol,2010,28(21):3491-3497.

[26] IYER RV,POKURI VK,GROMAN A,et al. A multicenter phase II study of gemcitabine,capecitabine,and bevacizumab for locally advanced or metastatic biliary tract cancer[J]. Am J Clin Oncol,2018,41(7):649-655.

[27] BENGALA C,BERTOLINI F,MALAVASI N,et al. Sorafenib in patients with advanced biliary tract carcinoma:A phase II trial[J]. Br J Cancer,2010,102(1):68-72.

[28] EL-KHOUEIRY AB,RANKIN CJ,BEN-JOSEF E,et al.SWOG 0514:A phase II study of sorafenib in patients with unresectable or metastatic gallbladder carcinoma and cholangiocarcinoma[J]. Invest New Drugs, 2012, 30(4):1646-1651.

[29] EL-KHOUEIRY AB,RANKIN CJ,SIEGEL AB,et al. S0941:A phase 2 SWOG study of sorafenib and erlotinib in patients with advanced gallbladder carcinoma or cholangiocarcinoma[J]. Br J Cancer,2014,110(4):882-887.

[30] LEE JK,CAPANU M,O’REILLY EM,et al. A phase II study of gemcitabine and cisplatin plus sorafenib in patients with advanced biliary adenocarcinomas[J]. Br J Cancer,2013,109(4):915-919.

[31] PAN TT,WANG W,JIA WD,et al. A single-center experience of sorafenib monotherapy in patients with advanced intrahepatic cholangiocarcinoma[J]. Oncol Lett,2017,13(5):2957-2964.

[32] LUO X,JIA W,HUANG Z,et al. Effectiveness and safety of sorafenib in the treatment of unresectable and advanced intrahepatic cholangiocarcinoma:A pilot study[J]. Oncotarget,2017,8(10):17246-17257.

[33] STRUMBERG D,SCHULTHEIS B. Regorafenib for cancer[J].Expert Opin Investig Drugs,2012,21(6):879-889.

[34] SUN W,PATEL A,NORMOLLE D,et al. A phase 2 trial of regorafenib as a single agent in patients with chemotherapy-refractory,advanced,and metastatic biliary tract adenocarcinoma[J]. Cancer,2019,125(6):902-909.

[35] ROY S,NARANG BK,RASTOGI SK,et al. A novel multiple tyrosine-kinase targeted agent to explore the future perspectives of anti-angiogenic therapy for the treatment of multiple solid tumors:Cabozantinib[J]. Anticancer Agents Med Chem,2015,15(1):37-47.

[36] YAKES FM,CHEN J,TAN J,et al. Cabozantinib(XL184),a novel MET and VEGFR2 inhibitor,simultaneously suppresses metastasis,angiogenesis,and tumor growth[J]. Mol Cancer Ther,2011,10(12):2298-2308.

[37] GOYAL L,ZHENG H,YURGELUN MB,et al. A phase 2 and biomarker study of cabozantinib in patients with advanced cholangiocarcinoma[J]. Cancer,2017,123(11):1979-1988.

[38] STERNBERG CN,DAVIS ID,MARDIAK J,et al. Pazopanib in locally advanced or metastatic renal cell carcinoma:Results of a randomized phase III trial[J]. J Clin Oncol,2010,28(6):1061-1068.

[39] SHROFF RT,YARCHOAN M,O’CONNOR A,et al. The oral VEGF receptor tyrosine kinase inhibitor pazopanib in combination with the MEK inhibitor trametinib in advanced cholangiocarcinoma[J]. Br J Cancer,2017,116(11):1402-1407.

[40] WEDGE SR,KENDREW J,HENNEQUIN LF,et al. AZD2171:A highly potent,orally bioavailable,vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer[J]. Cancer Res,2005,65(10):4389-4400.

[41] VALLE JW,WASAN H,LOPES A,et al. Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer(ABC-03):A randomised phase 2 trial[J]. Lancet Oncol,2015,16(8):967-978.

[42] VAETEEWOOTTACHARN K,KARIYA R,DANA P,et al. Inhibition of carbonic anhydrase potentiates bevacizumab treatment in cholangiocarcinoma[J]. Tumour Biol,2016,37(7):9023-9035.

[43] YOKOI K,KOBAYASHI A,MOTOYAMA H,et al. Survival pathway of cholangiocarcinoma via AKT/m TOR signaling to escape RAF/MEK/ERK pathway inhibition by sorafenib[J]. Oncol Rep,2018,39(2):843-850.

[44] LOZANO E,MACIAS RIR,MONTE MJ,et al. Causes of h OCT1-dependent cholangiocarcinoma resistance to sorafenib and sensitization by tumor-selective gene therapy[J]. Hepatology,2019,70(4):1246-1261.

[45] MOSADEGHI S,LIU B,BHUKET T,et al. Sex-specific and race/ethnicity-specific disparities in cholangiocarcinoma incidence and prevalence in the USA:An updated analysis of the2000-2011 surveillance,epidemiology and end results registry[J]. Hepatol Res,2016,46(7):669-677.

[46] PUTRA J,de ABREU FB,PETERSON JD,et al. Molecular profiling of intrahepatic and extrahepatic cholangiocarcinoma using next generation sequencing[J]. Exp Mol Pathol,2015,99(2):240-244.

[47] WELZEL TM,GRAUBARD BI,EL-SERAG HB,et al. Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United States:A population-based case-control study[J]. Clin Gastroenterol Hepatol,2007,5(10):1221-1228.

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