Journal
CANCER CELL
Volume 34, Issue 6, Pages 954-+Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2018.11.007
Keywords
-
Categories
Funding
- 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]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available