尼妥珠单抗的放疗增敏研究现状及进展

doi:10.11904/j.issn.1002-3070.2015.03.012

摘要/Abstract

摘要：

大量研究表明,EGFR信号通路与放疗抵抗相关,许多恶性肿瘤高度表达EGFR。EGFR阻断成为放疗增敏的途径之一。作为第一个由中国和古巴合作研制的EGFR单克隆抗体,尼妥珠单抗有其独特的临床特性,其联合放疗在头颈部肿瘤、食管癌和高级别脑胶质瘤等肿瘤中得到了广泛的研究及探索,本文就尼妥珠单抗放疗增敏的研究现状及进展做一综述。

关键词: 尼妥珠单抗, 放射敏感性, 肿瘤

Abstract:

With data support from abundant research,epithelial growth factor receptor(EGFR)signaling pathway is associated with radiotherapy resistance.EGFR inhibition has become one of Methods to increase radiosensitivity.As the first EGFR monoclonal antibody developed by China and Cuba,nimotuzumab demonstrates its distinct clinical characteristics and has been extensively explored in head and neck cancer,esophageal cancer,high grade glioma.This article mainly reviews the present situation and recent advances on the radiosensitivity research of nimotuzumab.

Key words: Nimotuzumab, Radiosensitivity, Cancer

中图分类号:

R730.55

滕凯^1,2, 张用¹综述, 刘莉¹审校. 尼妥珠单抗的放疗增敏研究现状及进展[J]. 实用肿瘤学杂志, 2015, 29(3): 245-248.

TENG Kai,ZHANG Yong,LIU Li. Present situation and advances on the nimotuzumab related radiosensitivity research[J]. PRACTICAL ONCOLOGY JOURNAL, 2015, 29(3): 245-248.

参考文献

1 Delaney G,Jacob S,Featherstone C,et al.The role of radiotherapy in cancer treatment:estimating optimal utilization from a review of evidence-based clinical guidelines[J].Cancer,2005,104(6):1129-1137.
2 Crombet-Ramos T,Rak J,Perez R,et al.Antiproliferative,antiangiogenic and proapoptotic activity of h-R3:A humanized anti-EGFR antibody[J].Int J Cancer,2002,101(6):567-575.
3 Liccardi G,Hartley JA,Hochhauser D.EGFR nuclear translocation modulates DNA repair following cisplatin and ionizing radiation treatment[J].Cancer Res,2011,71(3):1103-1114.
4 Dittmann K,Mayer C,Rodemann HP.Inhibition of radiation-induced EGFR nuclear import by C225(Cetuximab)suppresses DNA-PK activity[J].Radiother Oncol,2005,76(2):157-161.
5 Ishiguro Y,Ishiguro H,Miyamoto H.Epidermal growth factor receptor tyrosine kinase inhibition up-regulates interleukin-6 in cancer cells and induces subsequent development of interstitial pneumonia[J].Oncotarget,2013,4(4):550-559.
6 Diaz Miqueli A,Rolff J,Lemm M,et al.Radiosensitisation of U87MG brain tumours by anti-epidermal growth factor receptor monoclonal antibodies[J].Br J Cancer,2009,100(6):950-958.
7 Dittmann K,Mayer C,Fehrenbacher B,et al.Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase[J].J Biol Chem,2005,280(35):31182-31189.
8 Garrido G,Tikhomirov IA,Rabasa A,et al.Bivalent binding by intermediate affinity of nimotuzumab:a contribution to explain antibody clinical profile[J].Cancer Biol Ther,2011,11(4):373-382.
9 Khambata-Ford S,Harbison CT,Hart LL,et al.Analysis of potential predictive markers of cetuximab benefit in BMS099,a phase III study of cetuximab and first-line taxane/carboplatin in advanced non-small-cell lung cancer[J].J Clin Oncol,2010,28(6):918-927.
10 Diaz Miqueli A,Blanco R,Garcia B,et al.Biological activity in vitro of anti-epidermal growth factor receptor monoclonal antibodies with different affinities[J].Hybridoma(Larchmt),2007,26(6):423-431.
11 Das AK,Sato M,Story MD,et al.Non-small-cell lung cancers with kinase domain mutations in the epidermal growth factor receptor are sensitive to ionizing radiation[J].Cancer Res,2006,66(19):9601-9608.
12 Crombet T,Osorio M,Cruz T,et al.Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients[J].J Clin Oncol,2004,22(9):1646-1654.
13 Schmidt-Ullrich RK,Contessa JN,Lammering G,et al.ERBB receptor tyrosine kinases and cellular radiation responses[J].Oncogene,2003,22(37):5855-5865.
14 Avila MA,Velasco JA,Cho C,et al.Hyperactive autocrine loop mediated by a NDF-related factor in neoplastic hamster embryo fibroblasts expressing an activated cph oncogene[J].Oncogene,1995,10(5):963-971.
15 Ramos-Suzarte M,Lorenzo-Luaces P,Lazo NG,et al.Treatment of malignant,non-resectable,epithelial origin esophageal tumours with the humanized anti-epidermal growth factor antibody nimotuzumab combined with radiation therapy and chemotherapy[J].Cancer Biol Ther,2012,13(8):600-605.
16 Akashi Y,Okamoto I,Iwasa T,et al.Enhancement of the antitumor activity of ionising radiation by nimotuzumab,a humanised monoclonal antibody to the epidermal growth factor receptor,in non-small cell lung cancer cell lines of differing epidermal growth factor receptor status[J].Br J Cancer,2008,98(4):749-755.
17 Qu YY,Hu SL,Xu XY,et al.Nimotuzumab enhances the radiosensitivity of cancer cells in vitro by inhibiting radiation-induced DNA damage repair[J].PLoS One,2013,8(8):e70727.
18 Wang M,Morsbach F,Sander D,et al.EGF receptor inhibition radiosensitizes NSCLC cells by inducing senescence in cells sustaining DNA double-strand breaks[J].Cancer Res,2011,71(19):6261-6269.
19 Song H,Pan B,Yi J,et al.Featured article:autophagic activation with nimotuzumab enhanced chemosensitivity and radiosensitivity of esophageal squamous cell carcinoma[J].Exp Biol Med(Maywood),2014,239(5):529-541.
20 Zhao L,He LR,Xi M,et al.Nimotuzumab promotes radiosensitivity of EGFR-overexpression esophageal squamous cell carcinoma cells by upregulating IGFBP-3[J].J Transl Med,2012,10(12):249-257.
21 Zhang KL,Han L,Chen LY,et al.Blockage of a miR-21/EGFR regulatory feedback loop augments anti-EGFR therapy in glioblastomas[J].Cancer Lett,2014,342(1):139-149.
22 Zhang KL,Zhou X,Han L,et al.MicroRNA-566 activates EGFR signaling and its inhibition sensitizes glioblastoma cells to nimotuzumab[J].Mol Cancer,2014,13(3):63-73.
23 Bussink J,Kaanders JH,van der Kogel AJ.Microenvironmental transformations by VEGF-and EGF-receptor inhibition and potential implications for responsiveness to radiotherapy[J].Radiother Oncol,2007,82(1):10-17.
24 Reddy BK,Lokesh V,Vidyasagar MS,et al.Nimotuzumab provides survival benefit to patients with inoperable advanced squamous cell carcinoma of the head and neck:a randomized,open-label,phase IIb,5-year study in Indian patients[J].Oral Oncol,2014,50(5):498-505.
25 黄晓东,易俊林,高黎,等.抗表皮生长因子受体单克隆抗体h-R3联合放疗治疗晚期鼻咽癌的Ⅱ期临床研究[J].中华肿瘤杂志,2007,29(3):197-201.
26 Liang J,Wu G,Zhao L,et al.Nimotuzumab combined with radiotherapy for esophageal cancer:preliminary study of a Phase II clinical trial[J].Onco Targets Ther,2013,6(11):1589-1596.
27 Viana-Pereira M,Lopes JM,Little S,et al.Analysis of EGFR overexpression,EGFR gene amplification and the EGFRvIII mutation in portuguese high-grade gliomas[J].Anticancer Res,2008,28(2a):913-920.
28 Ramos TC,Figueredo J,Catala M,et al.Treatment of high-grade glioma patients with the humanized anti-epidermal growth factor receptor(EGFR)antibody h-R3:report from a phase I/II trial[J].Cancer Biol Ther,2006,5(4):375-379.
29 Solomon MT,Selva JC,Figueredo J,et al.Radiotherapy plus nimotuzumab or placebo in the treatment of high grade glioma patients:results from a randomized,double blind trial[J].BMC Cancer,2013,13:299.
30 Hong J,Peng Y,Liao Y,et al.Nimotuzumab prolongs survival in patients with malignant gliomas:A phase I/II clinical study of concomitant radiochemotherapy with or without nimotuzumab[J].Exp Ther Med,2012,4(1):151-157.
31 Cabanas R,Saurez G,Rios M,et al.Treatment of children with high grade glioma with nimotuzumab:a 5-year institutional experience[J].MAbs,2013,5(2):202-207.
32 Massimino M,Biassoni V,Miceli R,et al.Results of nimotuzumab and vinorelbine,radiation and re-irradiation for diffuse pontine glioma in childhood[J].J Neurooncol,2014,118(2):305-312.
33 Shin HK,Kim MS,Jeong JH.Combination effect of nimotuzumab with radiation in colorectal cancer cells[J].J Korean Soc Ther Radiol Oncol,2010,28(3):147-154.
34 Bebb G,Smith C,Rorke S,et al.Phase I clinical trial of the anti-EGFR monoclonal antibody nimotuzumab with concurrent external thoracic radiotherapy in Canadian patients diagnosed with stage IIb,III or IV non-small cell lung cancer unsuitable for radical therapy[J].Cancer Chemother Pharmacol,2011,67(4):837-845.
35 Choi HJ,Sohn JH,Lee CG,et al.A phase I study of nimotuzumab in combination with radiotherapy in stages IIB-IV non-small cell lung cancer unsuitable for radical therapy:Korean results[J].Lung Cancer,2011,71(1):55-59.
36 Macias A,Neninger E,Santiesteban E,et al.Preliminary results of a phase II clinical trial of the anti-EGFR monoclonal antibody Nimotuzumab in combination with whole brain radiation therapy in patients diagnosed with advanced non-small cell lung cancer tumors unresectable brain metastases[J].Ejc Supplements,2008,6(12):160-161.
37 Strumberg D,Schultheis B,Scheulen ME,et al.Phase II study of nimotuzumab,a humanized monoclonal anti-epidermal growth factor receptor(EGFR)antibody,in patients with locally advanced or metastatic pancreatic cancer[J].Invest New Drugs,2012,30(3):1138-1143.
38 周凤睿,陈公琰.酪氨酸激酶受体EphA7在恶性肿瘤中的研究进展[J].实用肿瘤

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