Annotation Detail
Information
- Associated Genes
- KRAS
- Associated Variants
-
KRAS MUTATION
KRAS MUTATION - Associated Disease
- cancer
- Source Database
- CIViC Evidence
- Description
- Preclinical study analyzing the differential response to MEK Inhibitors in KRAS and BRAF mutant cancer cell lines and mouse xenografts. Efficacy of MEK inhibitors (GDC-0623 and G-573) in KRAS-driven tumours is mediated by a hydrogen-bond interaction with S212 in MEK that is critical for blocking MEK feedback phosphorylation by wild-type RAF. This mechanism was distinct from GDC-0973 which is less potent in KRAS mutant tumors. Overall, this work indicates that MEK inhibitors with this mechanism of action will be most effective in patients with both BRAF and KRAS mutations.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1140
- Gene URL
- https://civic.genome.wustl.edu/links/genes/30
- Variant URL
- https://civic.genome.wustl.edu/links/variants/336
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Cancer
- Evidence Direction
- Supports
- Drug
- MEK Inhibitor GDC-0623,G-573
- Evidence Level
- D
- Clinical Significance
- Sensitivity/Response
- Pubmed
- 23934108
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| G-573 | Sensitivity | true |
| MEK Inhibitor GDC-0623 | Sensitivity | true |