Annotation Detail

Information
Associated Genes
ERBB2
Associated Variants
ERBB2 AMPLIFICATION ( ENST00000269571.10 )
ERBB2 AMPLIFICATION ( ENST00000269571.10 )
Associated Disease
Her2-receptor positive breast cancer
Source Database
CIViC Evidence
Description
In 5 trastuzumab resistant HER2 overexpressing breast cancer cell lines, combination of the pan-PI3K inhibitor XL147 (pilaralisib) and trastuzumab treatment induced cell death to similar or greater levels than XL147 alone. In three trastuzumab resistant cell lines tested, colony formation in matrigel was markedly inhibited by combination treatment. Apoptotic markers were apparent with combination treatment. In athymic mice, trastuzumab resistant cell line HR6 was used in tumor xenografts and tumors were allowed to form. Mice subsequently treated with trastuzumab or XL147 showed continued tumor growth without marked difference from control, while combination treatment essentially halted tumor growth rate.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1448
Gene URL
https://civic.genome.wustl.edu/links/genes/20
Variant URL
https://civic.genome.wustl.edu/links/variants/306
Rating
4
Evidence Type
Predictive
Disease
Her2-receptor Positive Breast Cancer
Evidence Direction
Supports
Drug
Pilaralisib,Trastuzumab
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
23204226
Drugs
Drug NameSensitivitySupported
PilaralisibSensitivitytrue
TrastuzumabSensitivitytrue