Annotation Detail
Information
- Associated Genes
- MTOR
- Associated Variants
-
MTOR E2014K + E2419K
MTOR E2014K + E2419K - Associated Disease
- transitional cell carcinoma
- Source Database
- CIViC Evidence
- Description
- A phase 1 clinical trial identified a patient with chemotherapy-refractory urothelial carcinoma who had complete radiographic response lasting 14 months after combined everolimus and pazopanib treatment. This patient was exome sequenced and two mutations co-occurring in MTOR were identified. Expression of these mutations in HEK293T cells demonstrated these were activating mutations. The authors propose that these two activating mutations are the reason for the dramatic response to mTOR inhibition and considered them as "biologically plausible" to confer sensitivity to everolimus.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1438
- Gene URL
- https://civic.genome.wustl.edu/links/genes/2073
- Variant URL
- https://civic.genome.wustl.edu/links/variants/572
- Rating
- 2
- Evidence Type
- Predictive
- Disease
- Urothelial Carcinoma
- Evidence Direction
- Supports
- Drug
- Pazopanib,Everolimus
- Evidence Level
- C
- Clinical Significance
- Sensitivity/Response
- Pubmed
- 24625776
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Everolimus | Sensitivity | true |
| Pazopanib | Sensitivity | true |