Investigational EGFR-targeted therapy in head and neck squamous cell carcinoma.
Investigational EGFR-targeted therapy in head and neck squamous cell carcinoma.
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DOI：
10.1517/13543781003769844
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发表时间：
2010-06
影响因子：
6.1
通讯作者：
Grandis JR
中科院分区：
文献类型：
--
作者：
Cassell A;Grandis JR
表皮生长因子受体（EGFR）是头颈部鳞状细胞癌（HNSCC）的治疗靶点。靶向egfr的单克隆抗体西妥昔单抗（™Erbitux）于2006年获得fda批准用于HNSCC。与使用小分子抑制剂抑制EGFR酪氨酸激酶功能或通过反义策略下调蛋白表达相比，抗体方法有效性的分子基础尚不完全清楚。我们进行了文献检索，以确定阐明几种靶向HNSCC中EGFR的方法（单克隆抗体、酪氨酸激酶抑制剂、反义方法和配体毒素偶联物）的作用机制的研究。单克隆抗体通过受体内吞作用和宿主免疫防御的募集来抑制肿瘤生长。酪氨酸激酶抑制剂与酪氨酸激酶结构域的ATP结合袋结合，抑制信号传导。反义方法以高特异性降低EGFR表达，尽管药物递送仍然存在问题。配体-毒素缀合物促进毒素的进入和核糖体的adp -核糖基化，从而抑制翻译。阐明这些不同策略抑制EGFR功能的机制可能会促进HNSCC更有效治疗的发展，并使从EGFR抑制中获益的个体能够得到前瞻性的识别。
The epidermal growth factor receptor (EGFR) is an established therapeutic target in head and neck squamous cell carcinoma (HNSCC). The EGFR-targeting monoclonal antibody cetuximab (™Erbitux) was FDA-approved for use in HNSCC in 2006. The molecular basis for the efficacy of an antibody approach compared with inhibition of EGFR tyrosine kinase function using small molecule inhibitors, or downregulation of protein expression via antisense strategies remains incompletely understood. A literature search was performed to identify studies elucidating mechanisms of action of several approaches to targeting EGFR in HNSCC (monoclonal antibodies, tyrosine kinase inhibitors, antisense approaches, and ligand toxin conjugates). Monoclonal antibodies decrease tumor growth via receptor endocytosis and recruitment of host immune defenses. Tyrosine kinase inhibitors bind to the ATP binding pocket of the tyrosine kinase domain, inhibiting signaling. Antisense approaches decrease EGFR expression with high specificity although drug delivery remains problematic. Ligand-toxin conjugates facilitate the entry of toxin and the ADP-ribosylation of the ribosome, thereby inhibiting translation. Elucidation mechanisms by which these different strategies inhibit EGFR function may enhance the development of more effective treatments for HNSCC and enable prospective identification of individuals who will benefit from EGFR inhibition.
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影响因子：
51.1
作者：
Cohen, Ezra E. W.;Davis, Darren W.;Karrison, Theodore G.;Seiwert, Tanguy Y.;Wong, Stuart J.;Nattam, Sreenivasa;Kozloff, Mark F.;Clark, Joseph I.;Yan, Duen-Hwa;Liu, Wen;Pierce, Carolyn;Dancey, Janet E.;Stenson, Kerstin;Blair, Elizabeth;Dekker, Allison;Vokes, Everett E.
通讯作者：
Vokes, Everett E.
影响因子：
5.7
作者：
Dawson, Jessica P.;Bu, Zimei;Lemmon, Mark A.
通讯作者：
Lemmon, Mark A.
DOI：
10.1073/pnas.0708148104
发表时间：
2007-10-23
影响因子：
11.1
作者：
Ebos, John M. L.;Lee, Christina R.;Kerbel, Robert S.
通讯作者：
Kerbel, Robert S.
影响因子：
158.5
作者：
Bonner, JA;Harari, PM;Ang, KK
通讯作者：
Ang, KK
影响因子：
11.2
作者：
Bocci, G;Man, S;Kerbel, RS
通讯作者：
Kerbel, RS