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AMG 479, a fully human anti-insulin-like growth factor receptor type I monoclonal antibody, inhibits the growth and survival of pancreatic carcinoma cells.AMG 479，一种全人源抗胰岛素样生长因子受体 I 型单克隆抗体，可抑制胰腺癌细胞的生长和存活。
Mol Cancer Ther. 2009 May;8(5):1095-105. doi: 10.1158/1535-7163.MCT-08-1171. Epub 2009 Apr 14.
2
Platinum-based chemotherapy plus cetuximab in head and neck cancer.铂类化疗联合西妥昔单抗治疗头颈癌。
N Engl J Med. 2008 Sep 11;359(11):1116-27. doi: 10.1056/NEJMoa0802656.
3
Increasing methotrexate resistance by combination of active-site mutations in human dihydrofolate reductase.通过人二氢叶酸还原酶活性位点突变组合增加甲氨蝶呤耐药性。
J Mol Biol. 2007 Oct 26;373(3):599-611. doi: 10.1016/j.jmb.2007.07.076. Epub 2007 Aug 17.
4
FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab.FCGR2A和FCGR3A基因多态性与接受单药西妥昔单抗治疗的表皮生长因子受体表达型转移性结直肠癌患者的临床结局相关。
J Clin Oncol. 2007 Aug 20;25(24):3712-8. doi: 10.1200/JCO.2006.08.8021.
5
Insulin-like growth factor receptor as a therapeutic target in head and neck cancer.胰岛素样生长因子受体作为头颈癌的治疗靶点
Clin Cancer Res. 2007 Jul 15;13(14):4291-9. doi: 10.1158/1078-0432.CCR-06-2040.
6
Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy.一项开放标签、非对照、多中心II期研究，旨在评估西妥昔单抗单药治疗对铂类治疗无效的复发和/或转移性头颈部鳞状细胞癌患者的疗效和毒性。
J Clin Oncol. 2007 Jun 1;25(16):2171-7. doi: 10.1200/JCO.2006.06.7447.
7
Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200.贝伐单抗联合奥沙利铂、氟尿嘧啶和亚叶酸钙（FOLFOX4）用于既往治疗过的转移性结直肠癌：东部肿瘤协作组E3200研究结果
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Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer.单独使用紫杉醇-卡铂或联合贝伐单抗治疗非小细胞肺癌。
N Engl J Med. 2006 Dec 14;355(24):2542-50. doi: 10.1056/NEJMoa061884.
9
Insulin-like growth factor-1 receptor and ligand targeting in head and neck squamous cell carcinoma.胰岛素样生长因子-1受体及配体靶向治疗头颈部鳞状细胞癌
Cancer Lett. 2007 Apr 18;248(2):269-79. doi: 10.1016/j.canlet.2006.08.004. Epub 2006 Sep 22.
10
Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas.表皮生长因子受体基因拷贝数增加与头颈部鳞状细胞癌的不良预后相关。
J Clin Oncol. 2006 Sep 1;24(25):4170-6. doi: 10.1200/JCO.2006.07.2587.

胰岛素样生长因子-1 受体抑制剂 AMG-479 治疗西妥昔单抗耐药的头颈部鳞状细胞癌。

Insulin-like growth factor-1 receptor inhibitor, AMG-479, in cetuximab-refractory head and neck squamous cell carcinoma.

机构信息

Division of Hematology/Oncology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

出版信息

Head Neck. 2011 Dec;33(12):1804-8. doi: 10.1002/hed.21478. Epub 2010 Jul 22.

DOI:10.1002/hed.21478
PMID:20652976
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3111896/
Abstract

BACKGROUND

Recurrent head and neck squamous cell carcinoma (HNSCC) remains a difficult cancer to treat. Here, we describe a patient with HNSCC who had complete response to methotrexate (MTX) after progressing on multiple cytotoxic agents, cetuximab, and AMG-479 (monoclonal antibody against insulin-like growth factor-1 receptor [IGF-1R]).

METHODS

The clinical information was collected by a retrospective medical record review under an Institutional Review Board-approved protocol. From 4 tumors and 2 normal mucosal epithelia, global gene expression, and IGF-1R and dihydrofolate reductase (DHFR) protein levels were determined.

RESULTS

Effective target inhibition in the tumor was confirmed by the decreased protein levels of total and phospho-IGF-1R after treatment with AMG-479. Decreased level of DHFR and conversion of a gene expression profile associated with cetuximab-resistance to cetuximab-sensitivity were also observed.

CONCLUSION

This suggests that the combination of AMG-479 and MTX or cetuximab may be a promising therapeutic approach in refractory HNSCC.

摘要

背景

复发性头颈部鳞状细胞癌（HNSCC）仍然是一种难以治疗的癌症。在这里，我们描述了一名 HNSCC 患者，在进展为多种细胞毒性药物、西妥昔单抗和 AMG-479（针对胰岛素样生长因子-1 受体 [IGF-1R] 的单克隆抗体）后，对甲氨蝶呤（MTX）有完全反应。

方法

通过机构审查委员会批准的协议进行回顾性病历审查收集临床信息。从 4 个肿瘤和 2 个正常黏膜上皮中，测定了全球基因表达以及 IGF-1R 和二氢叶酸还原酶（DHFR）蛋白水平。

结果

通过 AMG-479 治疗后，总 IGF-1R 和磷酸化 IGF-1R 的蛋白水平降低，证实了肿瘤中有效的靶抑制。还观察到 DHFR 水平降低以及与西妥昔单抗耐药相关的基因表达谱向西妥昔单抗敏感的转换。

结论

这表明 AMG-479 和 MTX 或西妥昔单抗的联合可能是复发性 HNSCC 的一种有前途的治疗方法。