Identification of kinases activated by multiple pro-angiogenic growth factors.
Identification of kinases activated by multiple pro-angiogenic growth factors.
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DOI：
10.3389/fphar.2022.1022722
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发表时间：
2022
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
抗血管生成治疗开始于抑制VEGF信号传导的努力，VEGF信号传导被认为是驱动肿瘤血管生成的唯一因素。已经清楚的是，在肿瘤血管形成过程中，有更多的促血管生成生长因子可以替代VEGF。这导致了同时靶向多种生长因子受体的多激酶抑制剂的开发。这些抑制剂比单一疗法表现更好，迄今为止，没有多激酶抑制剂靶向已知参与促血管生成信号传导的所有受体，并且不可避免地发生耐药性。鉴于大量的促血管生成生长因子的鉴定，可能不可能同时靶向所有促血管生成生长因子受体。在这里，我们寻找激酶的目标，其中一些可能是细胞内本地化，这是至关重要的内皮细胞增殖，无论使用的生长因子。我们开发了一种定量内皮细胞增殖试验，并将其与“激酶组回归”或KIR（一种最近开发的能够鉴定影响定量表型的激酶的方法）结合联合收割机。我们报告了KIR所涉及的激酶，并提供了它们在内皮细胞增殖中的重要性的正交证据。我们的方法可能指向一种新的策略，以开发一种更完整的抗血管生成的封锁。
Antiangiogenic therapy began as an effort to inhibit VEGF signaling, which was thought to be the sole factor driving tumor angiogenesis. It has become clear that there are more pro-angiogenic growth factors that can substitute for VEGF during tumor vascularization. This has led to the development of multi-kinase inhibitors which simultaneously target multiple growth factor receptors. These inhibitors perform better than monotherapies yet to date no multi-kinase inhibitor targets all receptors known to be involved in pro-angiogenic signaling and resistance inevitably occurs. Given the large number of pro-angiogenic growth factors identified, it may be impossible to simultaneously target all pro-angiogenic growth factor receptors. Here we search for kinase targets, some which may be intracellularly localized, that are critical in endothelial cell proliferation irrespective of the growth factor used. We develop a quantitative endothelial cell proliferation assay and combine it with “kinome regression” or KIR, a recently developed method capable of identifying kinases that influence a quantitative phenotype. We report the kinases implicated by KIR and provide orthogonal evidence of their importance in endothelial cell proliferation. Our approach may point to a new strategy to develop a more complete anti-angiogenic blockade.
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DOI：
10.1056/nejmoa1510016
发表时间：
2015-11-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Choueiri TK;Escudier B;Powles T;Mainwaring PN;Rini BI;Donskov F;Hammers H;Hutson TE;Lee JL;Peltola K;Roth BJ;Bjarnason GA;Géczi L;Keam B;Maroto P;Heng DY;Schmidinger M;Kantoff PW;Borgman-Hagey A;Hessel C;Scheffold C;Schwab GM;Tannir NM;Motzer RJ;METEOR Investigators
通讯作者：
METEOR Investigators
影响因子：
8.8
作者：
Na, Yi Rang;Kwon, Jung Won;Seok, Seung Hyeok
通讯作者：
Seok, Seung Hyeok
影响因子：
64.5
作者：
Gujral TS;Chan M;Peshkin L;Sorger PK;Kirschner MW;MacBeath G
通讯作者：
MacBeath G
影响因子：
8
作者：
Cao, Joan;Zhu, Zhou;Wei, Ping
通讯作者：
Wei, Ping
DOI：
10.1073/pnas.1403080111
发表时间：
2014-04-01
影响因子：
11.1
作者：
Gujral, Taranjit Singh;Peshkin, Leonid;Kirschner, Marc W.
通讯作者：
Kirschner, Marc W.