Small molecule profiling to define synergistic EGFR inhibitor combinations in head and neck squamous cell carcinoma.
Small molecule profiling to define synergistic EGFR inhibitor combinations in head and neck squamous cell carcinoma.
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DOI：
10.1002/hed.27018
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发表时间：
2022-05
期刊：
影响因子：
--
通讯作者：
Brenner JC
中科院分区：
文献类型：
--
作者：
Michmerhuizen NL;Ludwig ML;Birkeland AC;Nimmagadda S;Zhai J;Wang J;Jewell BM;Genouw D;Remer L;Kim D;Foltin SK;Bhangale A;Kulkarni A;Bradford CR;Swiecicki PL;Carey TE;Jiang H;Brenner JC
头颈部鳞状细胞癌(HNSCC)是一种存活率低的衰弱疾病。尽管针对表皮生长因子受体(EGFR)的抗体西妥昔单抗在某些情况下提高了存活率，但反应有限，提示需要替代方法。我们进行了高通量药物筛选，在对EGFR抑制剂单一疗法耐药的模型中识别基于EGFR抑制剂的临床晚期抑制剂的协同组合，然后对优先排序的协同组合进行下游验证试验。从我们的筛选中，我们重新发现了已知的与FGFR或IGF-1R抑制剂广泛有效的协同EGFR抑制剂组合，还发现了仅在部分模型中有效的与XIAP抑制剂和DNMT抑制剂的新协同组合。在概念上，我们的数据确定了新的协同组合，值得在未来的研究中进行评估，并表明一些组合，尽管具有高度的协同作用，但需要平行的伴随诊断开发才能在患者中有效地推进。
Head and neck squamous cell carcinoma (HNSCC) is a debilitating disease with poor survival. Although epidermal growth factor receptor (EGFR)‐targeting antibody cetuximab improves survival in some settings, responses are limited suggesting that alternative approaches are needed. We performed a high throughput drug screen to identify EGFR inhibitor‐based synergistic combinations of clinically advanced inhibitors in models resistant to EGFR inhibitor monotherapies, and then performed downstream validation experiments on prioritized synergistic combinations. From our screen, we re‐discovered known synergistic EGFR inhibitor combinations with FGFR or IGF‐1R inhibitors that were broadly effective and also discovered novel synergistic combinations with XIAP inhibitor and DNMT inhibitors that were effective in only a subset of models. Conceptually, our data identify novel synergistic combinations that warrant evaluation in future studies, and suggest that some combinations, although highly synergistic, will require parallel companion diagnostic development to be effectively advanced in patients.
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DOI：
10.1186/bcr2328
发表时间：
2009
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Foster FM;Owens TW;Tanianis-Hughes J;Clarke RB;Brennan K;Bundred NJ;Streuli CH
通讯作者：
Streuli CH
影响因子：
5.7
作者：
Anisuzzaman, Abu Syed Md;Haque, Abedul;Amin, A. R. M. Ruhul
通讯作者：
Amin, A. R. M. Ruhul
DOI：
10.1158/1078-0432.ccr-14-3357
发表时间：
2015-10-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Göke F;Franzen A;Hinz TK;Marek LA;Yoon P;Sharma R;Bode M;von Maessenhausen A;Lankat-Buttgereit B;Göke A;Golletz C;Kirsten R;Boehm D;Vogel W;Kleczko EK;Eagles JR;Hirsch FR;Van Bremen T;Bootz F;Schroeck A;Kim J;Tan AC;Jimeno A;Heasley LE;Perner S
通讯作者：
Perner S
影响因子：
51.1
作者：
Giralt, Jordi;Trigo, Jose;VanderWalde, Ari
通讯作者：
VanderWalde, Ari
影响因子：
3.3
作者：
Daniel, Filipe I.;Alves, Soraia R.;Modolo, Filipe
通讯作者：
Modolo, Filipe