Annotation Detail
Information
- Associated Genes
- PIK3CA
- Associated Variants
-
PIK3CA MUTATION
PIK3CA MUTATION - Associated Disease
- breast cancer
- Source Database
- CIViC Evidence
- Description
- Three PI3K mutant breast cancer cell lines were rendered resistant to PI3K inhibitors (BYL719 or GDC-0941), and a panel of 42 inhibitor compounds was tested on the cells for ability to resensitize the cells to PI3K inhibition. The CDK4/6 inhibitor ribociclib (LEE011) acted synergistically with PI3K inhibitor to reduce viability in all three resistant cell lines. In a panel of 12 PIK3CA mutant and 10 wild type cell lines, synergistic effects between P110alpha inhibitor BYL719 and ribociclib were significantly stronger (weighted synergy score calculation, ANOVA, p=0.012) in PIK3CA mutant cells, indicating variant specific sensitization. Mouse xenografts of 4 different PIK3CA mutant breast cancer cells resistant to PI3K inhibitor showed stronger regression under dual PI3K inhibitor and ribociclib treatment than with either treatment alone.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1600
- Gene URL
- https://civic.genome.wustl.edu/links/genes/37
- Variant URL
- https://civic.genome.wustl.edu/links/variants/311
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Breast Cancer
- Evidence Direction
- Supports
- Drug
- Ribociclib,Phosphatidylinositide 3-Kinase Inhibitor
- Evidence Level
- D
- Clinical Significance
- Sensitivity/Response
- Pubmed
- 25002028
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Phosphatidylinositide 3-Kinase Inhibitor | Sensitivity | true |
| Ribociclib | Sensitivity | true |