期刊
CANCER CELL
卷 34, 期 6, 页码 954-+出版社
CELL PRESS
DOI: 10.1016/j.ccell.2018.11.007
关键词
-
资金
- US National Institutes of Health (MD Anderson Cancer Center) [P30CA016672]
- MD Anderson Cancer Center-China Medical University and Hospital Sister Institution Fund
- Ministry of Health and Welfare, China Medical University Hospital Cancer Research Center of Excellence [MOHW107-TDU-B-212-114024, MOHW107-TDU-B-112015]
- Center for Biological Pathways
- Chang Gung Memorial Hospital [CMRPG3D1911]
Multiple mechanisms of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been identified in EGFR-mutant non-small cell lung cancer (NSCLC); however, recurrent resistance to EGFR TKIs due to the heterogeneous mechanisms underlying resistance within a single patient remains a major challenge in the clinic. Here, we report a role of nuclear protein kinase C delta (PKC delta) as a common axis across multiple known TKI-resistance mechanisms. Specifically, we demonstrate that TKI-inactivated EGFR dimerizes with other membrane receptors implicated in TKI resistance to promote PKC delta nuclear translocation. Moreover, the level of nuclear PKC delta is associated with TKI response in patients. The combined inhibition of PKC delta and EGFR induces marked regression of resistant NSCLC tumors with EGFR mutations.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据