Insulin/Insulin-like growth factors in cancer: new roles for the aryl hydrocarbon receptor, tumor resistance mechanisms, and new blocking strategies.
Insulin/Insulin-like growth factors in cancer: new roles for the aryl hydrocarbon receptor, tumor resistance mechanisms, and new blocking strategies.
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DOI：
10.3389/fendo.2015.00012
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发表时间：
2015
影响因子：
5.2
通讯作者：
Tomblin JK
中科院分区：
文献类型：
--
作者：
Salisbury TB;Tomblin JK
胰岛素样生长因子1受体(IGF1R)和胰岛素受体(IR)是在癌细胞中表达的受体酪氨酸激酶。不同的研究结果表明，肿瘤的增殖和生存依赖于IGF1R和IR，抑制IGF1R和IR会导致细胞增殖减少和细胞死亡增加。已用于实体肿瘤的分子靶向治疗包括抗IGF1R抗体、抗IGF1/IGF2抗体和抑制IGF1R和IR激酶活性的小分子抑制剂。抗IGF1R阻断抗体分子基础的新进展表明，它们是有偏向的激动剂，可促进某些癌细胞中IGF1与整合素β3受体的结合。我们最近的报告表明，药理上的芳香烃受体(AHR)配体抑制乳腺癌细胞对IGFS的反应，这表明靶向AHR可能对依赖胰岛素/IGF信号转导的肿瘤的增殖和生存有好处。将讨论IGF1R/IR在癌症中的新方面，如偏向激动剂、整合素β3信号、促肾上腺皮质激素受体和新的治疗靶向策略。
The insulin-like growth factor 1 receptor (IGF1R) and the insulin receptor (IR) are receptor tyrosine kinases that are expressed in cancer cells. The results of different studies indicate that tumor proliferation and survival is dependent on the IGF1R and IR, and that their inhibition leads to reductions in proliferation and increases in cell death. Molecular targeting therapies that have been used in solid tumors include anti-IGF1R antibodies, anti-IGF1/IGF2 antibodies, and small molecule inhibitors that suppress IGF1R and IR kinase activity. New advances in the molecular basis of anti-IGF1R blocking antibodies reveal they are biased agonists and promote the binding of IGF1 to integrin β3 receptors in some cancer cells. Our recent reports indicate that pharmacological aryl hydrocarbon receptor (AHR) ligands inhibit breast cancer cell responses to IGFs, suggesting that targeting AHR may have benefit in cancers whose proliferation and survival are dependent on insulin/IGF signaling. Novel aspects of IGF1R/IR in cancer, such as biased agonism, integrin β3 signaling, AHR, and new therapeutic targeting strategies will be discussed.
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DOI：
10.1155/2013/104850
发表时间：
2013
期刊：
ISRN endocrinology
影响因子：
--
作者：
Salisbury TB;Morris GZ;Tomblin JK;Chaudhry AR;Cook CR;Santanam N
通讯作者：
Santanam N
影响因子：
11.8
作者：
King, Helen;Aleksic, Tamara;Haluska, Paul;Macaulay, Valentine M.
通讯作者：
Macaulay, Valentine M.
DOI：
10.1073/pnas.0810221106
发表时间：
2009-02-17
影响因子：
11.1
作者：
Klinakis, Apostolos;Szabolcs, Matthias;Efstratiadis, Argiris
通讯作者：
Efstratiadis, Argiris
影响因子：
10.5
作者：
Fernández, AM;Kim, JK;Le Roith, D
通讯作者：
Le Roith, D
影响因子：
3.8
作者：
Denison, Michael S.;Soshilov, Anatoly A.;Zhao, Bin
通讯作者：
Zhao, Bin