Identification and therapeutic intervention of coactivated anaplastic lymphoma kinase, fibroblast growth factor receptor 2, and ephrin type-A receptor 5 kinases in hepatocellular carcinoma

doi:10.1002/hep.29792

	Identification and therapeutic intervention of coactivated anaplastic lymphoma kinase, fibroblast growth factor receptor 2, and ephrin type-A receptor 5 kinases in hepatocellular carcinoma
	Wang, Xin; Zhang, Minmin; Ping, Fangfang; Liu, Hongchun; Sun, Jingya; Wang, Yueqin; Shen, Aijun; Ding, Jian; Geng, Meiyu
刊名	Hepatology (Baltimore, Md.)
	2018-01-21
ISSN号	1527-3350
DOI	10.1002/hep.29792
文献子类	Article
英文摘要	Though kinase inhibitors have been heavily investigated in the clinic to combat advanced hepatocellular carcinoma (HCC), clinical outcomes have been disappointing overall, which may be due to the absence of kinase-addicted subsets in HCC patients. Recently, strategies that simultaneously inhibit multiple kinases are increasingly appreciated in HCC treatment, yet they are challenged by the dynamic nature of the kinase networks. This study aims to identify clustered kinases that may cooperate to drive the malignant growth of HCC. We show that anaplastic lymphoma kinase, fibroblast growth factor receptor 2, and ephrin type-A receptor 5 are the essential kinases that assemble into a functional cluster to sustain the viability of HCC cells through downstream protein kinase B-dependent, extracellular signal-regulated kinase-dependent, and p38-dependent signaling pathways. Their coactivation is associated with poor prognosis for overall survival in about 13% of HCC patients. Moreover, their activities are tightly regulated by heat shock protein 90 (Hsp90). Thereby Combined kinase inhibition or targeting of heat shock protein 90 led to significant therapeutic responses both in vitro and in vivo.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/266744]
专题	药物化学研究室
作者单位	Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
推荐引用方式 GB/T 7714	Wang, Xin,Zhang, Minmin,Ping, Fangfang,et al. Identification and therapeutic intervention of coactivated anaplastic lymphoma kinase, fibroblast growth factor receptor 2, and ephrin type-A receptor 5 kinases in hepatocellular carcinoma[J]. Hepatology (Baltimore, Md.),2018.
APA	Wang, Xin.,Zhang, Minmin.,Ping, Fangfang.,Liu, Hongchun.,Sun, Jingya.,...&Geng, Meiyu.(2018).Identification and therapeutic intervention of coactivated anaplastic lymphoma kinase, fibroblast growth factor receptor 2, and ephrin type-A receptor 5 kinases in hepatocellular carcinoma.Hepatology (Baltimore, Md.).
MLA	Wang, Xin,et al."Identification and therapeutic intervention of coactivated anaplastic lymphoma kinase, fibroblast growth factor receptor 2, and ephrin type-A receptor 5 kinases in hepatocellular carcinoma".Hepatology (Baltimore, Md.) (2018).