Annotation Detail
Information
- Associated Genes
- BRAF
- Associated Variants
-
BRAF p.Val640Glu (p.V640E)
(
ENST00000288602.11,
ENST00000496384.7,
ENST00000644969.2,
ENST00000646891.2 )
BRAF p.Val640Glu (p.V640E) ( ENST00000288602.11, ENST00000496384.7, ENST00000644969.2, ENST00000646891.2 ) - Associated Disease
- colorectal cancer
- Source Database
- CIViC Evidence
- Description
- In a mouse model of BRAF V600E colorectal cancer, western blots from tumors in mice treated with BRAF inhibitor GDC-0879 and PI3K/mTOR inhibitor BEZ235 showed stronger reduction in phospho-Akt and phospho-S6 than PI3K/mTOR inhibitor alone, and combination inhibition also resulted in stronger phospho-ERK inhibition in tumors than did BRAF inhibition alone. Increased apoptosis in tumors was seen in dual treatment conditions with increased TUNEL-positive cells. In vehicle treated mice, area of colon covered by tumor increased, while treatment with single agent inhibitors caused growth inhibition resulting in no change in colon area covered by tumors. Administration of dual inhibitors induced tumor regression apparent in a decrease of colonic area covered by tumors over the course of treatment.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1428
- Gene URL
- https://civic.genome.wustl.edu/links/genes/5
- Variant URL
- https://civic.genome.wustl.edu/links/variants/12
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Colorectal Cancer
- Evidence Direction
- Supports
- Drug
- GDC-0879,Dactolisib
- Evidence Level
- D
- Clinical Significance
- Sensitivity/Response
- Pubmed
- 23549875
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Dactolisib | Sensitivity | true |
| GDC-0879 | Sensitivity | true |