Annotation Detail
Information
- Associated Genes
- KRAS
- Associated Variants
-
KRAS MUTATION
KRAS MUTATION - Associated Disease
- cancer
- Source Database
- CIViC Evidence
- Description
- CDK1 was identified in a preclinical siRNA screen to identify targets in KRAS mutant tumors. Cell viability was evaluated following knockdown of 834 genes in isogenic LIM1215 colorectal cancer cell lines harboring wildtype (parental), G12S, G12D or G12V KRAS. 6 targets identified by this screen were evaluated in a second set of isogenic colorectal cancer cell lines (SW48) harboring wildtype (parental), G12S, G12D, G12V or G13D KRAS where only CDK1 knockdown more profoundly reduced survival in mutant cells compared to wildtype. Results were validated in 5 KRAS mutant (BRAF WT) and 10 KRAS WT colorectal cancer cell lines. Chemical inhibition of CDK1 by AZD5438 in KRAS mutant vs WT pancreatic and colorectal cancer cell lines showed increased efficacy in mutant cell lines. Finally, AZD5438 reduced tumor growth induced by SW620 (KRAS p.G12V) colorectal tumour cells xenografted into immunodeficient mice.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1183
- Gene URL
- https://civic.genome.wustl.edu/links/genes/30
- Variant URL
- https://civic.genome.wustl.edu/links/variants/336
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Cancer
- Evidence Direction
- Supports
- Drug
- AZD5438
- Evidence Level
- D
- Clinical Significance
- Sensitivity/Response
- Pubmed
- 26881434
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| AZD5438 | Sensitivity | true |