Annotation Detail
Information
- Associated Genes
- EGFR
- Associated Variants
-
EGFR p.Gly465Arg (p.G465R)
(
ENST00000275493.7,
ENST00000342916.7,
ENST00000344576.7,
ENST00000450046.2,
ENST00000455089.5 )
EGFR p.Gly465Arg (p.G465R) ( ENST00000455089.5, ENST00000275493.7, ENST00000342916.7, ENST00000344576.7, ENST00000450046.2 ) - Associated Disease
- colorectal cancer
- Source Database
- CIViC Evidence
- Description
- An EGFR G465R mutation (22% of mutant alleles) was detected in a biopsy from one patient which had been previously treated with cetuximab in the analysis of 15 patients with refractory, metastatic CRC after cetuximab/panitumumab, prior to Sym004 treatment. Treatment of this patient with Sym004 yielded disease stabilization lasting 15 weeks. Sym004 is a 1:1 mixture of two non-overlapping anti-EGFR monoclonal antibodies. In vitro analysis in the murine fibroblast cell line NIH3T3 with ectopic expression of EGFR mutations S492R, R451C, K467T, and G465R showed that Sym004 effectively bound to all mutants, whereas cetuximab and panitumumab did not effectively bind to all mutants. In-vitro, Sym004 inhibited growth of S492R and G465R EGFR mutant cell lines. In-vivo analysis of S492R and G465R mutant cell lines showed regression of S492R and tumor growth delay of G465R mutant cell lines. G465R mutant cell lines were resistant to treatment with panitumumab or cetuximab in-vitro.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1058
- Gene URL
- https://civic.genome.wustl.edu/links/genes/19
- Variant URL
- https://civic.genome.wustl.edu/links/variants/443
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Colorectal Cancer
- Evidence Direction
- Supports
- Drug
- Panitumumab,Cetuximab
- Evidence Level
- C
- Clinical Significance
- Resistance
- Pubmed
- 26888827
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Cetuximab | Resitance or Non-Reponse | true |
| Panitumumab | Resitance or Non-Reponse | true |