Molecular Profile Detail

Profile Name AKT1 E17K
Gene Variant Detail

AKT1 E17K (gain of function)

Relevant Treatment Approaches Akt Inhibitor (Pan) Akt1 Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
AKT1 E17K melanoma sensitive Akt Inhibitor (Pan) GSK2141795 Preclinical - Cell culture Actionable In a preclinical study, Uprosertib (GSK2141795) inhibited the growth of melanoma cells harboring AKT1 E17K in culture (PMID: 24735930). 24735930
AKT1 E17K triple-receptor negative breast cancer sensitive Akt Inhibitor (Pan) Capivasertib Clinical Study Actionable In a clinical study, a patient with triple-receptor negative breast cancer harboring AKT1 E17K demonstrated a partial response when treated with AZD5363 (PMID: 28489509). 28489509
AKT1 E17K ovarian endometrial cancer sensitive Akt Inhibitor (Pan) Capivasertib Phase I Actionable In a Phase I clinical study, a patient with endometrioid ovarian carcinoma harboring AKT1 E17K had a sustained partial response to AZD5363 for more than two years (PMID: 26351323). 26351323
AKT1 E17K granulosa cell tumor sensitive Akt Inhibitor (Pan) Capivasertib Phase I Actionable In a Phase I trial, a patient with ovarian granulosa cell tumor cancer harboring subclonal AKT E17K demonstrated an overall tumor regression of 24% when treated with AZD5363, which lasted 253 days (PMID: 28489509). 28489509
AKT1 E17K Her2-receptor negative breast cancer sensitive Akt Inhibitor (Pan) Ipatasertib Phase I Actionable In a Phase I trial, a patient with ERBB2 (HER2)-receptor negative breast cancer harboring AKT1 E17K demonstrated a complete metabolic response when treated with Ipatasertib (GDC-0068) (PMID: 27872130). 27872130
AKT1 E17K breast cancer sensitive Akt1 Inhibitor BAY1125976 Preclinical - Pdx Actionable In a preclinical study, BAY1125976 induced complete tumor regression in a patient-derived xenograft (PDX) model of breast cancer harboring AKT E17K (PMID: 27699769). 27699769
AKT1 E17K breast papillary carcinoma sensitive Akt Inhibitor (Pan) Capivasertib Phase I Actionable In a Phase I clinical trial, a patient with ER-positive, ERBB2 (HER2)-negative papillary breast carcinoma harboring AKT1 E17K had a sustained partial response to AZD5363 (PMID: 26351323). 26351323
AKT1 E17K Her2-receptor negative breast cancer predicted - sensitive Akt Inhibitor (Pan) Capivasertib Phase II Actionable In a Phase II (MATCH) trial, Capivasertib (AZD5363) treatment resulted in partial response in 23% (8/35) of patients with advanced solid tumors harboring AKT1 E17K mutation, 6 of the patients achieved partial response had hormone receptor-positive, Erbb2 (Her2)-negative breast cancer (PMID: 30429128; NCT02465060). 30429128
AKT1 E17K cancer sensitive Akt Inhibitor (Pan) GSK2141795 Preclinical Actionable In a preclinical study, the pan AKT inhibitor GSK2141795 displayed similar levels of inhibition against ATK1 E17K (activating mutation) as ATK1 wild-type (PMID: 24978597). 24978597
AKT1 E17K endometrial cancer sensitive Akt Inhibitor (Pan) Capivasertib Clinical Study Actionable In a clinical study, two patients with endometrial cancer harboring AKT1 E17K demonstrated a partial response when treated with AZD5363 (PMID: 28489509). 28489509
AKT1 E17K uterus leiomyosarcoma predicted - sensitive Akt Inhibitor (Pan) Capivasertib Phase II Actionable In a Phase II (MATCH) trial, Capivasertib (AZD5363) treatment resulted in partial response in a patient with uterus leiomyosarcoma harboring AKT1 E17K mutation (PMID: 30429128; NCT02465060). 30429128
AKT1 E17K Advanced Solid Tumor sensitive Akt Inhibitor (Pan) Capivasertib Phase II Actionable In a Phase II (MATCH) trial, Capivasertib (AZD5363) treatment resulted in partial response in 23% (8/35) and stable disease in 46% (16/35) of patients with advanced solid tumors harboring AKT1 E17K mutation (PMID: 30429128; NCT02465060). 30429128
AKT1 E17K Advanced Solid Tumor sensitive Akt Inhibitor (Pan) Capivasertib Phase I Actionable In a Phase I trial, Capivasertib (AZD5363) demonstrated safety and preliminary antitumor activity in patients with advanced solid tumors, resulted in stable disease in 27% (10/37) of patients and partial response in two patients, both of whom harbored an AKT1 E17K mutation (PMID: 26931343; NCT01353781). 26931343 detail...
AKT1 E17K parotid gland cancer predicted - sensitive Akt Inhibitor (Pan) Capivasertib Phase II Actionable In a Phase II (MATCH) trial, Capivasertib (AZD5363) treatment resulted in stable disease over 21 months in a patient with an oncocytic carcinoma of the parotid gland harboring AKT1 E17K mutation (PMID: 30429128; NCT02465060). 30429128
AKT1 E17K lung adenocarcinoma sensitive Akt Inhibitor (Pan) Capivasertib Clinical Study Actionable In a clinical study, a patient with lung adenocarcinoma harboring AKT1 E17K demonstrated a partial response when treated with AZD5363 (PMID: 28489509). 28489509
AKT1 E17K anal canal cancer sensitive Akt1 Inhibitor BAY1125976 Preclinical - Pdx Actionable In a preclinical study, treatment with BAY1125976 reduced tumor growth and resulted in partial tumor regression or stable disease in anal cancer patient-derived xenograft (PDX) models harboring AKT1 E17K (PMID: 27699769). 27699769 detail...
AKT1 E17K breast cancer sensitive Akt Inhibitor (Pan) Capivasertib Preclinical Actionable In a preclinical study, AZD5363 inhibited growth and colony formation of breast cancer cells expressing AKT E17K in cell culture and in xenografts as well as breast cancer explant models harboring AKT E17K (PMID: 26351323). 26351323
AKT1 E17K breast cancer sensitive Akt Inhibitor (Pan) Capivasertib Clinical Study Actionable In a clinical study, four patients with ESR1-positive breast cancer harboring AKT1 E17K demonstrated a partial response when treated with AZD5363 (PMID: 28489509). 28489509
AKT1 E17K endometrial adenocarcinoma predicted - sensitive Akt Inhibitor (Pan) Capivasertib Phase II Actionable In a Phase II (MATCH) trial, Capivasertib (AZD5363) treatment resulted in partial response in a patient with endometrioid adenocarcinoma harboring AKT1 E17K mutation (PMID: 30429128; NCT02465060). 30429128
AKT1 E17K endometrial cancer sensitive Akt Inhibitor (Pan) ARQ092 Preclinical - Cell line xenograft Actionable In a preclinical study, an endometrial cell line xenograft model harboring AKT E17K was sensitive to ARQ092, demonstrating inhibition of tumor growth (PMID: 26469692). 26469692
AKT1 E17K estrogen-receptor positive breast cancer predicted - sensitive Akt Inhibitor (Pan) Capivasertib Phase I Actionable In a Phase I trial, Capivasertib (AZD5363) treatment resulted in confirmed partial response in four and unconfirmed partial response in two patients with ESR1-positive breast cancer harboring AKT1 E17K (PMID: 28489509; NCT01226316). 28489509
AKT1 E17K cervical cancer sensitive Akt Inhibitor (Pan) Capivasertib Clinical Study Actionable In a clinical study, a patient with cervical cancer harboring AKT1 E17K demonstrated a partial response when treated with AZD5363 (PMID: 28489509). 28489509
AKT1 E17K meningothelial meningioma sensitive Akt Inhibitor (Pan) Capivasertib Clinical Study Actionable In a clinical case study, a patient with meningothelial meningioma harboring AKT1 E17K demonstrated stable disease and some tumor regression when treated with AZD5363 (PMID: 28376212). 28376212
AKT1 E17K endometrial cancer sensitive Akt Inhibitor (Pan) ARQ 751 Preclinical - Cell line xenograft Actionable In a preclinical study, an endometrial cell line xenograft model harboring AKT E17K was sensitive to ARQ 751, demonstrating inhibition of tumor growth (PMID: 26469692). 26469692
Clinical Trial Phase Therapies Title Recruitment Status
NCT03310541 Phase I Capivasertib AZD5363 + Enzalutamide AZD5363 + Fulvestrant AZD5363 in Patients With Advanced Solid Tumors Harboring AKT Mutations Recruiting
NCT01915576 Phase I BAY1125976 Phase I Dose Escalation Study With an Allosteric AKT 1/2 Inhibitor in Patients Completed