Annotation Detail

Information
Associated Genes
PTEN
Associated Variants
PTEN DELETION ( ENST00000371953.8 )
PTEN DELETION ( ENST00000371953.8 )
Associated Disease
Her2-receptor positive breast cancer
Source Database
CIViC Evidence
Description
Knockdown of PTEN in trastuzumab sensitive HER2 breast cancer BT474 cells induced trastuzumab resistance. PTEN null cells treated with PI3K inhibitor LY294002 also did not show substantial inhibition, but co-treatment with trastuzumab and LY294002 induced growth inhibition comparable to trastuzumab alone in normal BT474 cells. BT474 mouse xenograft tumors were injected with PTEN antisense (AS) oligonucleotides and this resulted in trastuzumab resitance. Co-treatment of PTEN AS tumor mice with LY294002 and trastuzumab inhibited tumor growth in comparison to PTEN AS tumors treated with trastuzumab or LY294002 alone.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1455
Gene URL
https://civic.genome.wustl.edu/links/genes/41
Variant URL
https://civic.genome.wustl.edu/links/variants/214
Rating
3
Evidence Type
Predictive
Disease
Her2-receptor Positive Breast Cancer
Evidence Direction
Supports
Drug
PI3K/BET Inhibitor LY294002,Trastuzumab
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
15324695
Drugs
Drug NameSensitivitySupported
PI3K/BET Inhibitor LY294002Sensitivitytrue
TrastuzumabSensitivitytrue