UNASSIGNED: @entity7171 , a well established oncogenic member of @entity12841 family, is among the most intensely investigated kinase drug targets. In contrast to hotspot mutations of @entity12841 , few mutations of @entity7171 locate in activation loop within kinase domain. We previously reported the molecular mechanism underlying hyper kinase activity of HER2 @entity68900 , a mutation located in activation loop. However, its tumorigenicity in vivo and relevant therapeutics remain to be determined. Here, we report for the first time that HER2H878Y was tumorigenic in vivo in @entity2220 transgenic @entity19 model. Induced expression of HER2H878Y in lung epithelial compartments resulted in formation of poorly differentiated @entity2220 with @entity133 ( @entity133 ) features. Strikingly, we found that these @entity5 depended on continuous expression of HER2H878Y for maintenance. Typical @entity7171 downstream signaling mediators, including PLCy1, @entity23117 and @entity1994 , were hyperactivated in @entity2 . More importantly, administration of @entity36447 , a @entity4149 kinase inhibitor (TKI), efficiently shrank HER2H878Y driven @entity5 in transgenic @entity19 model. Moreover, we found that combinational treatment with @entity36447 and @entity3470 inhibitor, @entity3446 , showed a superior @entity137 to @entity68900 mutant transformed cells and enhanced activity to elicit apoptosis and inhibit growth in situ in tumorous area. Our work therefore showed that HER2 @entity68900 mutant was a reasonable drug target. Hence, our work supported the assessment of @entity36447 / @entity3446 treatment in clinical trials.

XXXX driven by gain-of-function @entity7171 @entity68900 mutant is highly sensitive to @entity7171 inhibitor.

@entity36447 :: ('MESH:C487932', 'Chemical') :: ['HKI-272', 'HKI272'] @entity137 :: ('MESH:D064420', 'Disease') :: ['cytotoxicity'] @entity12841 :: ('13649(Tax:10090)', 'Gene') :: ['EGFR'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumors'] @entity2 :: ('MESH:D008175', 'Disease') :: ['HER2H878Y driven lung tumors'] @entity68900 :: ('p|SUB|H|878|Y', 'ProteinMutation') :: ['H878Y'] @entity133 :: ('MESH:D002282', 'Disease') :: ['bronchioloalveolar carcinoma', 'BAC'] @entity3446 :: ('MESH:D020123', 'Chemical') :: ['Rapamycin', 'rapamycin'] @entity3470 :: ('21977(Tax:10090)', 'Gene') :: ['mTOR'] @entity1994 :: ('11651(Tax:10090)', 'Gene') :: ['AKT'] @entity7171 :: ('13866(Tax:10090)', 'Gene') :: ['HER2'] @entity23117 :: ('20850(Tax:10090)', 'Gene') :: ['STAT5'] @entity2220 :: ('MESH:C538231', 'Disease') :: ['lung adenocarcinoma'] @entity4149 :: ('D014443', 'Chemical') :: ['tyrosine']
@entity5 :: (MESH:D009369,Disease) :: ['Tumor']
