Annotation Detail

Information
Associated Genes
EGFR
Associated Variants
EGFR p.Thr790Met (p.T790M) ( ENST00000275493.7, ENST00000450046.2, ENST00000455089.5 )
EGFR p.Thr790Met (p.T790M) ( ENST00000275493.7, ENST00000450046.2, ENST00000455089.5 )
Associated Disease
lung non-small cell carcinoma
Source Database
CIViC Evidence
Description
In an in vitro study using purified EGFR protein, kinase activity was assayed and compared for wildtype EGFR, EGFR-T790M and EGFR-T790M/L858R using both reversible and irreversible TKI drugs. EFGR proteins with T790M or T790M/L858R mutations were more sensitive to afatinib treatment (IC50: 9.8nM and 24nM, respectively vs. IC50: >1000nM and >1000nM, respectively) compared to treatment with erlotinib or lapatinib treatment. In an in vitro study using NCI-H358 cells (wildtype EGFR) and NCI-H1975 cells (EGFR-L858R/T790M), inhibition of cell growth was used as an assay to determine sensitivity to tyrosine kinase inhibitor drugs. Cells with an EGFR L858R/T790M mutation demonstrated an improved response to afatinib (GI50: 42.0nM vs. >1000nM) compared to the same cells treated with erlotinib. However, IC50s were intermediate compared to a more potent pan-HER inhibitor.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/2164
Gene URL
https://civic.genome.wustl.edu/links/genes/19
Variant URL
https://civic.genome.wustl.edu/links/variants/34
Rating
2
Evidence Type
Predictive
Disease
Lung Non-small Cell Carcinoma
Evidence Direction
Supports
Drug
Afatinib
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
21732342
Drugs
Drug NameSensitivitySupported
AfatinibSensitivitytrue