AKT1 E17K mutation

aka AKT1 E17K, AKT1 mutation, E17K, AKT1-mutant

AKT1 E17K is a single hotspot mutation, in about 3 to 5 percent of hormone-receptor-positive breast cancers, that switches on the AKT kinase directly. It is one of the three alterations that qualify a patient for capivasertib.

The E17K substitution in the pleckstrin homology domain sends AKT1 to the membrane without PIP3. Capivasertib (Truqap) is labelled with fulvestrant for HR-positive HER2-negative advanced breast cancer with one or more PIK3CA, AKT1 or PTEN alterations as detected by an FDA-approved test (CAPItello-291); FoundationOne CDx carries the three-gene claim. AKT1 E17K also appears in endometrial and rarer cancers, where it is a trial marker only.

Part ofAKT· AKT1/2/3 All readouts

AKT: what it is and how drugs act on it · animated schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

In plain words · AKT is a central survival kinase downstream of PI3K, blocked by capivasertib in breast and now prostate cancer.

Sequencing 1 approval threshold

What it means for a patient

An AKT1 E17K result in hormone-receptor-positive breast cancer qualifies you for capivasertib with fulvestrant once hormone therapy has stopped working, the same as a PIK3CA mutation or PTEN loss would. Alpelisib and inavolisib are not approved for AKT1 mutations on their own.

Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.

Scoring rule

The AKT1 c.49G>A (p.E17K) substitution by sequencing of tumour tissue or plasma, reported with PIK3CA and PTEN as the capivasertib selection set.

“PIK3CA/AKT1/PTEN alterations”
FDA: List of FDA-Authorized Companion Diagnostic Devices

Thresholds used in approvals

Threshold	Drug	Cancer	Regulator	Source
AKT1 alteration (with PIK3CA and PTEN as the qualifying set)	Capivasertib	HR-positive / HER2-negative breast cancer	FDA	label

Drugs whose label names it

Capivasertib

Companion diagnostics (FDA list)

Device	Maker	Indication and sample	Drug	PMA / 510(k)
FoundationOne CDx	Foundation Medicine	Breast Cancer - Tissue	Capivasertib Fulvestrant	P170019/S048 (11/16/2023)

Tests that measure it

FoundationOne CDx Tempus xT and xT CDx FoundationOne CDx FoundationOne Liquid CDx Guardant360 CDx

Trials that name this readout

Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.