Annotation Detail
Information
- Associated Genes
- ERBB3
- Associated Variants
-
ERBB3 OVEREXPRESSION
(
ENST00000267101.8 )
ERBB3 OVEREXPRESSION ( ENST00000267101.8 ) - Associated Disease
- cancer
- Source Database
- CIViC Evidence
- Description
- Preclinical study in KRAS mutant lung and colon cancer models. A synthetic lethal screen identified ERBB3 blockade to confer sensitivity to MEK inhibitors. The dual EGFR-ERBB2 (both forming heterodimers with ERBB3) inhibitors afatinib and dacomitinib each showed strong synergy with MEK Inhibition (trametinib or selumetinib) in several KRAS mutant cell lines. MEK Inhibitors alone or the combination with gefitinib (EGFRi) or CP724714 (ERBB2i) showed strong synergy. Results were validated in-vivo. Basal ERBB3 expression was associated with higher synergy scores.
- Variant Origin
- N/A
- Variant Origin
- N/A
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1153
- Gene URL
- https://civic.genome.wustl.edu/links/genes/1733
- Variant URL
- https://civic.genome.wustl.edu/links/variants/289
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Cancer
- Evidence Direction
- Supports
- Drug
- Gefitinib,HER2 Inhibitor CP-724,714,Selumetinib
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 24685132
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| 714 | Resitance or Non-Reponse | true |
| Gefitinib | Resitance or Non-Reponse | true |
| HER2 Inhibitor CP-724 | Resitance or Non-Reponse | true |
| Selumetinib | Resitance or Non-Reponse | true |