Annotation Detail
Information
- Associated Genes
- ALK
- Associated Variants
- ALK EML4-ALK
- Associated Disease
- lung non-small cell carcinoma
- Source Database
- CIViC Evidence
- Description
- In preclinical work using H3122 NSCLC cells which contain the EML4-ALK variant 1, administration of the Hsp90 inhibitor IPI-504 caused marked decrease of EML4-ALK protein levels at concentrations lower than those used to knock down protein levels of drivers such as HER2 or EGFR in other cell lines, making it the most sensitive Hsp90 client protein the authors had encountered. IPI-504 treatment caused regression of H3122 tumors in nude mice, whereas Hsp90 inhibitors usually only cause growth inhibition in these models. Combined treatment of these mice with IPI-504 and crizotinib caused an even stronger tumor regression.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1203
- Gene URL
- https://civic.genome.wustl.edu/links/genes/1
- Variant URL
- https://civic.genome.wustl.edu/links/variants/5
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Lung Non-small Cell Carcinoma
- Evidence Direction
- Supports
- Drug
- Retaspimycin Hydrochloride,Crizotinib
- Evidence Level
- D
- Clinical Significance
- Sensitivity/Response
- Pubmed
- 21258415
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Crizotinib | Sensitivity | true |
| Retaspimycin Hydrochloride | Sensitivity | true |