Annotation Detail
Information
- Associated Genes
- ALK
- Associated Variants
- ALK EML4-ALK
- Associated Disease
- lung non-small cell carcinoma
- Source Database
- CIViC Evidence
- Description
- Transduction of Ba/F3 cells with EML4-ALK variant 1 causes IL3 independent growth. Incubation of EML4-ALK variant 1 transduced Ba/F3 cells with Hsp90 inhibitor 17-DMAG caused cell death that was reversible with IL3 addition, suggesting that 17-DMAG was effecting the EML4-ALK driver of IL3-independant proliferation, and that EML4-ALK variant 1 is a client protein of Hsp90. The degree of Hsp90 dependence, and targetability of EML4-ALK for Hsp90 inhibition, may vary among ALK fusion variants. Addition of crizotinib to 17-DMAG caused synergistic death effects, suggesting potential clinical benefit for this inhibitor combination in targeting EML4-ALK variant 1.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1206
- Gene URL
- https://civic.genome.wustl.edu/links/genes/1
- Variant URL
- https://civic.genome.wustl.edu/links/variants/5
- Rating
- 2
- Evidence Type
- Predictive
- Disease
- Lung Non-small Cell Carcinoma
- Evidence Direction
- Supports
- Drug
- Alvespimycin,Crizotinib
- Evidence Level
- D
- Clinical Significance
- Sensitivity/Response
- Pubmed
- 22912387
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Alvespimycin | Sensitivity | true |
| Crizotinib | Sensitivity | true |