Targeting EGFR exon 20 insertion mutations in non-small cell lung cancer.
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Embargo End Date
ICR Authors
Authors
Vyse, S
Huang, PH
Huang, PH
Document Type
Journal Article
Date
2019-03-08
Date Accepted
2019-02-13
Abstract
Inframe insertions of three or more base pairs in exon 20 of the epidermal growth factor receptor (EGFR) gene were among the first EGFR mutations to be identified as oncogenic drivers in non-small cell lung cancer (NSCLC). However, unlike the classical EGFR L858R point mutation or exon 19 deletions, which represent the majority of EGFR mutations in NSCLC, low frequency EGFR exon 20 insertion mutations are associated with de novo resistance to targeted EGFR inhibitors and correlate with a poor patient prognosis. Here, we review the developments over the last 5 years in which pre-clinical studies, including elucidation of the crystal structure of an EGFR exon 20 insertion mutant kinase, have revealed a unique mechanism of kinase activation and steric conformation that define the lack of response of these EGFR mutations to clinically approved EGFR inhibitors. The recent development of several novel small molecule compounds that selectively inhibit EGFR exon 20 insertions holds promise for future therapeutic options that will be effective for patients with this molecular subtype of NSCLC.
Citation
Signal transduction and targeted therapy, 2019, 4 pp. 5 - ?
Source Title
Publisher
SPRINGERNATURE
ISSN
2095-9907
eISSN
2059-3635
Collections
Research Team
Protein Networks
Molecular and Systems Oncology
Molecular and Systems Oncology