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 using a total of 3,530 shRNAs to target 518 human kinases identified ERBB3 knockdown to confer sensitivity of selumetinib-resistant H358 cells (NSCLC cell line) to the MEK inhibitor selumetinib. The dual EGFR-ERBB2 inhibitors afatinib and dacomitinib each showed synergy with MEK Inhibition via selumetinib in 4 KRAS mutant cell lines. Western blot evaluation of 9 NSCLC and 12 CRC cell lines showed ERBB3 expression correlated with the synergy score for combination afatinib and trametinib treatment. I.e. the synergy score was low in cells having low basal levels of ERBB3 protein and high for cells having high basal ERBB3 expression. Using selumetinib in patient-derived CRC xenografts or trametinib in NSCLC xenografts, MEK inhibition by selumetinib or trametinib in combination with afatinib more effectively inhibited increases in tumor volume than either monotherapy.
- Variant Origin
- N/A
- Variant Origin
- N/A
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1152
- Gene URL
- https://civic.genome.wustl.edu/links/genes/1733
- Variant URL
- https://civic.genome.wustl.edu/links/variants/289
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Cancer
- Evidence Direction
- Supports
- Drug
- Selumetinib,Afatinib
- Evidence Level
- D
- Clinical Significance
- Sensitivity/Response
- Pubmed
- 24685132
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Afatinib | Sensitivity | true |
| Selumetinib | Sensitivity | true |