Annotation Detail
Information
- Associated Genes
- MTOR
- Associated Variants
-
MTOR p.Ala2034Val (p.A2034V)
(
ENST00000361445.9,
ENST00000703140.1 )
MTOR p.Ala2034Val (p.A2034V) ( ENST00000361445.9, ENST00000703140.1 ) - Associated Disease
- breast cancer
- Source Database
- CIViC Evidence
- Description
- MCF-7 breast cancer cell line was exposed to mTOR inhibitor rapamycin until resistance developed. Deep sequencing revealed an MTOR A2034V mutation in the resistant clone (RR1). Downstream signalling was independent of inhibitor presence in these clones and expression of the mutation in MDA-MB-468 cells led to resistance to rapamycin but maintained sensistivity to AZD8055. A novel mTOR inhibitor RapaLink-1 was designed and showed efficacy in A2034V mTOR mutant cell lines in-vivo and in-vitro. AZD8055 also retained efficacy in these clones in xenograft.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1548
- Gene URL
- https://civic.genome.wustl.edu/links/genes/2073
- Variant URL
- https://civic.genome.wustl.edu/links/variants/610
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Breast Cancer
- Evidence Direction
- Does Not Support
- Drug
- MTOR Kinase Inhibitor AZD8055,RapaLink-1
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 27279227
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| MTOR Kinase Inhibitor AZD8055 | Resitance or Non-Reponse | false |
| RapaLink-1 | Resitance or Non-Reponse | false |