Annotation Detail
Information
- Associated Genes
- NRAS
- Associated Variants
-
NRAS MUTATION
NRAS MUTATION - Associated Disease
- melanoma
- Source Database
- CIViC Evidence
- Description
- In six NRAS mutant melanoma cell lines, concomitant use of MEK inhibitor and PI3K/mTOR inhibitor resulted in greater decrease in cell viability than either alone, with the synergistic effect being marked in 4/6 cell lines. MEK inhibitor JTP-74057 and PI3K/mTOR inhibitor GSK2126458 together induced synergistic increase in apoptotic Annexin V+/PI+ cells in these cell lines. Tumor xenografts in nude mice were established with 5 of the 6 cell lines. Effects of single agent treatment with JTP-74057 or GSK2126458 ranged from minor inhibition to tumor stasis, while dual inhibitor treatment showed synergistic effects in each case, with marked tumor reductions in 2/5 cases and the authors report one compete response in a MaMel301 cell line xenograft mouse.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1429
- Gene URL
- https://civic.genome.wustl.edu/links/genes/36
- Variant URL
- https://civic.genome.wustl.edu/links/variants/208
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Melanoma
- Evidence Direction
- Supports
- Drug
- Omipalisib,Trametinib
- Evidence Level
- D
- Clinical Significance
- Sensitivity/Response
- Pubmed
- 23431193
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Omipalisib | Sensitivity | true |
| Trametinib | Sensitivity | true |