Annotation Detail
Information
- Associated Genes
- ALK
- Associated Variants
- ALK p.Ile1171Thr (p.I1171T) ALK p.Ile1171Thr (p.I1171T)
- Associated Disease
- lung non-small cell carcinoma
- Source Database
- CIViC Evidence
- Description
- The MGH056-1 cell line was derived from an NSCLC patient with ALK-rearrangement who had progressed on crizotinib and then on alectinib. the cell line was also resistant to crizotinib and alectinib, and sequencing of ALK from the cell line revealed the I1171T mutation. Further testing of this mutation in BaF3 cells revealed that cells expressing EML4-ALk with I1171T mutation required 10x higher concentration to induce cell death than BaF3 cells with wild-type EML4-ALK. In contrast, ceritinib caused loss of viability in EML4-ALK wild-type and I1171T BaF3 cells at comparable concentrations. Ceritinib was also effective at killing MGH056-1 cells that were resistant to alectinib, and reduced Akt and ERK phosphorylation in these cells. Finally, administration of ceritinib to the crizotinib and alectinib resistant patient let to tumor regression and partial response lasting 7 months.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1284
- Gene URL
- https://civic.genome.wustl.edu/links/genes/1
- Variant URL
- https://civic.genome.wustl.edu/links/variants/527
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Lung Non-small Cell Carcinoma
- Evidence Direction
- Supports
- Drug
- Ceritinib
- Evidence Level
- C
- Clinical Significance
- Sensitivity/Response
- Pubmed
- 25228534
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Ceritinib | Sensitivity | true |