Annotation Detail

Information
Associated Genes
AKT1
Associated Variants
AKT1 p.Glu17Lys (p.E17K) ( ENST00000402615.6, ENST00000349310.7, ENST00000554848.5, ENST00000555528.5, ENST00000407796.7, ENST00000553797.2, ENST00000554192.6, ENST00000554581.5, ENST00000555458.6, ENST00000649815.2, ENST00000683722.1, ENST00000714123.1, ENST00000714130.1 )
AKT1 p.Glu17Lys (p.E17K) ( ENST00000349310.7, ENST00000402615.6, ENST00000407796.7, ENST00000553797.2, ENST00000554192.6, ENST00000554581.5, ENST00000554848.5, ENST00000555458.6, ENST00000555528.5, ENST00000649815.2, ENST00000683722.1, ENST00000714123.1, ENST00000714130.1 )
Associated Disease
cancer
Source Database
CIViC Evidence
Description
AKT1 E17K mutations are oncogenic and occur in many cancers at a low prevalence. We performed a multihistology basket study of AZD5363. 58 patients with advanced solid tumors were treated. In patients with AKT1 E17K-mutant tumors (n = 52) and a median of 5 lines of prior therapy, the median PFS was 5.5 months , 6.6 months and 4.2 months in patients with ER+ breast, gynecologic, and other solid tumors, respectively. In an exploratory biomarker analysis, imbalance of the AKT1 E17K-mutant allele, most frequently caused by copy-neutral loss-of-heterozygosity targeting the wild-type allele, was associated with longer PFS as was the presence of coincident PI3K pathway hotspot mutations. Persistent declines in AKT1 E17K in cfDNA were associated with improved PFS and response. Responses were not restricted to patients with detectable AKT1 E17K in pretreatment cfDNA.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/3039
Gene URL
https://civic.genome.wustl.edu/links/genes/2
Variant URL
https://civic.genome.wustl.edu/links/variants/4
Rating
4
Evidence Type
Predictive
Disease
Cancer
Evidence Direction
Supports
Drug
Capivasertib
Evidence Level
B
Clinical Significance
Sensitivity/Response
Pubmed
28489509
Drugs
Drug NameSensitivitySupported
CapivasertibSensitivitytrue