Journal
THERANOSTICS
Volume 6, Issue 8, Pages 1232-1243Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.14409
Keywords
epidermal growth factor receptor; EGFR; MAPK
Categories
Funding
- National Natural Science Foundation of China [81472537, 81502597]
- China Postdoctoral Science Foundation [2015M580338]
- State Key Laboratory of Oncogenes and Related Genes [91-14-18, 91-15-12]
- Collaborative Innovation Center for Translational Medicine at Shanghai Jiao Tong University School of Medicine
- Shanghai Institutions of Higher Learning
- Shanghai Rising-Star Program [16QA1403600]
Ask authors/readers for more resources
Both adaptive and acquired resistance significantly limits the efficacy of the epidermal growth factor receptor (EGFR) kinase inhibitors. However, the distinct or common mechanisms of adaptive and acquired resistance have not been fully characterized. Here, through systematic modeling of erlotinib resistance in lung cancer, we found that feedback reactivation of MAPK signaling following erlotinib treatment, which was dependent on the MET receptor, contributed to the adaptive resistance of EGFR inhibitors. Interestingly, acquired resistance to erlotinib was also associated with the MAPK pathway activation as a result of CRAF or NRAS amplification. Consequently, combined inhibition of EGFR and MAPK impeded the development of both adaptive and acquired resistance. These observations demonstrate that adaptive and acquired resistance to EGFR inhibitors can converge on the same pathway and credential cotargeting EGFR and MAPK as a promising therapeutic approach in EGFR mutant tumors.
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