Insulin-like growth factor-1 receptor inhibitor, AMG-479, in cetuximab-refractory head and neck squamous cell carcinoma.
Insulin-like growth factor-1 receptor inhibitor, AMG-479, in cetuximab-refractory head and neck squamous cell carcinoma.
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DOI：
10.1002/hed.21478
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发表时间：
2011-12
影响因子：
2.9
通讯作者：
Murphy, Barbara
中科院分区：
文献类型：
--
作者：
Chung, Christine H.;Pohlmann, Paula R.;Rothenberg, Mace L.;Burkey, Brian B.;Parker, Joel;Palka, Kevin;Aulino, Joseph;Puzanov, Igor;Murphy, Barbara
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，我们描述了一位HNSCC患者，在接受多种细胞毒性药物、西妥昔单抗和AMG-479（抗胰岛素样生长因子-1受体[IGF-1R]的单克隆抗体）治疗后，对甲氨蝶呤（MTX）有完全反应。临床信息是根据机构审查委员会批准的方案通过回顾性病历审查收集的。从4例肿瘤和2例正常粘膜上皮细胞中，检测整体基因表达、IGF-1R和二氢叶酸还原酶（DHFR）蛋白水平。AMG-479治疗后，总igf - 1r和磷酸化igf - 1r蛋白水平下降，证实了AMG-479在肿瘤中的有效抑制作用。还观察到DHFR水平的降低以及与西妥昔单抗耐药相关的基因表达谱转化为西妥昔单抗敏感。这表明AMG- 479联合MTX或西妥昔单抗可能是治疗难治性HNSCC的一种有希望的方法。
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]). 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. 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. This suggests that the combination of AMG- 479 and MTX or cetuximab may be a promising therapeutic approach in refractory HNSCC.
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