Molecular Profile Detail

Profile Name AKT1 S246F
Gene Variant Detail

AKT1 S246F (unknown)

Relevant Treatment Approaches

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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 NRAS G12D prostate cancer sensitive BAY1125976 Preclinical - Cell line xenograft Actionable In a preclinical study, BAY1125976 inhibited proliferation of a prostate cancer cell line harboring AKT E17K and NRAS G12D in culture, and demonstrated antitumor activity in xenograft models (PMID: 27699769). 27699769
AKT1 E17K KRAS wild-type BRAF wild-type colorectal cancer predicted - resistant Cetuximab + Irinotecan Case Reports/Case Series Actionable In a retrospective analysis, 100% (2/2) of colorectal carcinoma patients harboring an AKT1 E17K mutation and wild-type KRAS/BRAF demonstrated resistance to Erbitux (cetuximab) in combination with Camptosar (irinotecan) (PMID: 25714871). 25714871
AKT1 E17K FGFR3 Y373C urinary bladder cancer sensitive AZD4547 + Capivasertib Preclinical Actionable In a preclinical study, the combined therapy of AZD5363 and AZD4547 resulted in tumor regression in urinary bladder cancer xenograft models simultaneously harboring the mutations, AKT1 E17K and FGFR3 Y373C (PMID: 26351323). 26351323
AKT1 E17K BRAF V600X PTEN pos melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, expression of AKT1 E17K in a wild-type PTEN-expressing BRAF V600-mutant melanoma cell line conferred resistance to Zelboraf (vemurafenib) in culture (PMID: 24265152). 24265152
AKT1 E17K NRAS Q61R bladder carcinoma sensitive BAY1125976 Preclinical - Cell culture Actionable In a preclinical study, BAY1125976 inhibited Akt activation and downstream signaling in bladder cancer cell lines carrying both Akt1 E17K and Nras Q61R mutations (AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3685). detail...
AKT1 E17K uterus leiomyosarcoma predicted - sensitive 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 breast papillary carcinoma sensitive 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 Advanced Solid Tumor sensitive 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 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 lung adenocarcinoma predicted - sensitive Capivasertib Case Reports/Case Series Actionable In a Phase I trial, a patient with lung adenocarcinoma harboring AKT1 E17K demonstrated a partial response when treated with Capivasertib (AZD5363) (PMID: 28489509; NCT01226316). 28489509
AKT1 E17K endometrial adenocarcinoma predicted - sensitive 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 predicted - sensitive Capivasertib Case Reports/Case Series Actionable In a Phase I trial, two patients with endometrial cancer harboring AKT1 E17K demonstrated a partial response when treated with Capivasertib (AZD5363) (PMID: 28489509; NCT01226316). 28489509
AKT1 E17K triple-receptor negative breast cancer predicted - sensitive Capivasertib Case Reports/Case Series Actionable In a Phase I trial, a patient with triple-receptor negative breast cancer harboring AKT1 E17K demonstrated a partial response when treated with Capivasertib (AZD5363) (PMID: 28489509; NCT01226316). 28489509
AKT1 E17K cancer sensitive Uprosertib 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 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 breast cancer sensitive 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 parotid gland cancer predicted - sensitive 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 anal canal cancer sensitive 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 Capivasertib Case Reports/Case Series Actionable In a Phase I trial, four patients with ESR1-positive breast cancer harboring AKT1 E17K demonstrated a partial response when treated with Capivasertib (AZD5363) (PMID: 28489509; NCT01226316). 28489509
AKT1 E17K breast cancer sensitive Capivasertib Preclinical Actionable In a preclinical study, Capivasertib (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 Her2-receptor negative breast cancer sensitive 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 granulosa cell tumor sensitive Capivasertib Case Reports/Case Series 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 predicted - sensitive 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 endometrial cancer sensitive 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
AKT1 E17K meningothelial meningioma predicted - sensitive Capivasertib Case Reports/Case Series Actionable In a clinical case study, a patient with meningothelial meningioma harboring AKT1 E17K demonstrated stable disease and some tumor regression when treated with Capivasertib (AZD5363) (PMID: 28376212). 28376212
AKT1 E17K ovarian endometrial cancer sensitive 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 estrogen-receptor positive breast cancer predicted - sensitive Capivasertib Phase I Actionable In a Phase I trial, Capivasertib (AZD5363) treatment resulted in confirmed partial response in 20% (4/20) and unconfirmed partial response in 10% (2/20) of patients with ESR1-positive breast cancer harboring AKT1 E17K (PMID: 28489509; NCT01226316). 28489509
AKT1 E17K cervical cancer predicted - sensitive Capivasertib Case Reports/Case Series Actionable In a Phase I trial, a patient with cervical cancer harboring AKT1 E17K demonstrated a partial response when treated with Capivasertib (AZD5363) (PMID: 28489509; NCT01226316). 28489509
AKT1 E17K melanoma sensitive Uprosertib 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 amp Advanced Solid Tumor predicted - sensitive ONC201 Preclinical - Cell line xenograft Actionable In a preclinical study, ONC201 (TIC-10) inhibited Akt activation and induced apoptosis and tumor regression in a variety of cell line xenograft models (PMID: 23390247). 23390247
AKT1 act mut lymphoma no benefit Sirolimus Preclinical - Cell line xenograft Actionable In a preclinical study, Rapamune (sirolimus) treatment did not improve survival in cell line xenograft animal models of lymphoma overexpressing constitutively active Akt (PMID: 18708578). 18708578
AKT1 act mut lymphoma decreased response Doxorubicin Preclinical - Cell line xenograft Actionable In a preclinical study, lymphoma cells overexpressing constitutively active Akt demonstrated reduced sensitivity to Adriamycin (doxorubicin) treatment in cell line xenograft models (PMID: 18708578). 18708578
AKT1 act mut lymphoma predicted - sensitive Doxorubicin + Sirolimus Preclinical - Cell line xenograft Actionable In a preclinical study, Rapamune (sirolimus) and Adriamycin (doxorubicin) combination treatment resulted in improved survival and prolonged remission in cell line xenograft animal models of lymphoma overexpressing constitutively active Akt (PMID: 18708578). 18708578
AKT1 act mut Advanced Solid Tumor no benefit Triciribine Phase I Actionable In a Phase I trial, Triciribine (API-2) demonstrated safety, but lacked efficacy as a monotherapy in advanced solid tumor patients with activated Akt (PMID: 20644979). 20644979
AKT1 mutant endometrial cancer predicted - sensitive Temsirolimus Phase II Actionable In a retrospective study of a Phase II trial, Torisel (temsirolimus) treatment resulted in an increased progression-free survival (HR 0.16) and response rate (response difference 0.83) in advanced endometrial cancer patients harboring AKT1 mutations (PMID: 27016228). 27016228
AKT1 mutant triple-receptor negative breast cancer predicted - sensitive Capivasertib + Paclitaxel Phase II Actionable In a Phase II trial, Capivasertib (AZD5363) in combination with Taxol (paclitaxel) as first-line therapy resulted in improved median progression-free survival (9.3 vs 3.7 months, HR=0.30, p=0.01) compared to placebo in patients with metastatic triple-negative breast cancer harboring PIK3CA, AKT1, and/or PTEN mutations, but not in patients with wile-type PIK3CA, AKT1, and PTEN (5.3 vs 4.4 months, HR=1.13, p=0.61) (PMID: 30715161; NCT02423603). 30715161
AKT1 mutant triple-receptor negative breast cancer predicted - sensitive Ipatasertib + Paclitaxel Phase II Actionable In a Phase II trial, Ipatasertib (GDC-0068) in combination with Abraxane (paclitaxel) resulted in improved progression free survival (6.2 vs 4.9 months) compared to placebo in triple-receptor negative breast cancer patients harboring mutations in PIK3CA, AKT1, or PTEN (J Clin Oncol 35, 2017 (suppl; abstr 1009)). detail...
AKT1 mutant endometrial cancer sensitive GDC-0980 Phase II Actionable In a Phase II trial, Apitolisib (GDC-0980) was poorly tolerated, but demonstrated efficacy in endometrial cancer patients harboring mutations in PIK3CA, PTEN, or AKT1 (J Clin Oncol 32:5s, 2014 (suppl; abstr 5513)). detail...
AKT1 mutant invasive bladder transitional cell carcinoma predicted - resistant Cisplatin + Gemcitabine + Sorafenib Phase II Actionable In a Phase II trial, AKT1 mutations were more frequent in muscle-invasive urothelial bladder cancer patients that did not respond to Nexavar (sorafenib), Platinol (cisplatin) and Gemzar (gemcitabine) combination therapy than those who did respond (J Clin Oncol 35, 2017 (suppl 6S; abstract 345)). detail...
AKT1 Q79K BRAF V600X PTEN pos melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, expression of AKT1 Q79K in a wild-type PTEN-expressing BRAF V600-mutant melanoma cell line conferred resistance to Zelboraf (vemurafenib) in culture (PMID: 24265152). 24265152
AKT1 Q79K BRAF V600X PTEN pos melanoma sensitive MK2206 + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the combination of MK2206 and Zelboraf (vemurafenib) inhibited AKT activation and growth of PTEN-expressing BRAF V600-mutant melanoma cells expressing AKT1 Q79K in culture, with increased efficacy over either agent alone (PMID: 24265152). 24265152
AKT1 Q79K ovarian cancer predicted - sensitive Capivasertib Case Reports/Case Series Actionable In a Phase I trial, an ovarian cancer patient harboring AKT1 Q79K demonstrated tumor regression that lasted 14 months when treated with Capivasertib (AZD5363) (PMID: 28489509; NCT01226316). 28489509
AKT1 W80A Advanced Solid Tumor resistant MK2206 Preclinical - Cell culture Actionable In a preclinical study, transformed mouse adipocytes expressing human Akt1 W80A were resistant to the AKT inhibitor, MK-2206 (PMID: 25856301). 25856301
AKT1 W80A breast cancer resistant MK2206 Preclinical Actionable In a preclinical study, breast cancer cells expressing AKT1 W80A were resistant to MK2206 in culture, resulting in repression of induced cell death when compared to wild-type AKT1 (PMID: 25551293). 25551293
AKT1 P68_C77dup breast cancer sensitive Capivasertib Preclinical - Cell culture Actionable In a preclinical study, breast epithelial cells expressing AKT1 P68_C77dup demonstrated sensitivity by AZD5363 in culture, resulting in decreased cell survival (PMID: 29247016). 29247016
AKT1 wild-type cancer sensitive Uprosertib Preclinical Actionable In a preclinical study, GSK2141795 inhibited all isoforms of AKT in human cancer cell lines (PMID: 23795919). 23795919
AKT1 wild-type clear cell renal cell carcinoma sensitive Everolimus + RX-0201 Phase Ib/II Actionable In a Phase I/II trial, RX-0201 and Afinitor (everolimus) combination therapy resulted in stable disease in 40% (2/5) of patients with metastatic clear cell renal carcinoma (J Clin Oncol 34, 2016 (suppl 2S; abstr 550)). detail...
AKT1 wild-type ovarian cancer predicted - sensitive Uprosertib Phase I Actionable In a Phase I trial, GSK2141795 treatment resulted in Akt inhibition and clinical benefit in 27% (3/11) of ovarian cancer patients (PMID: 26429956). 26429956
AKT1 S266L FGFR1 amp lung cancer predicted - sensitive Uprosertib Preclinical - Cell culture Actionable In a preclinical study, lung cancer cells harboring FGFR1 amplification and AKT1 S266L demonstrated sensitivity to Uprosertib (GSK2141795) in culture, showing decreased phosphorylation of Akt1 targets and reduced cell growth (PMID: 30140389). 30140389
AKT1 S266L FGFR1 amp lung cancer predicted - resistant PD173074 Preclinical - Cell culture Actionable In a preclinical study, lung cancer cells harboring FGFR1 amplification demonstrated resistance to increasing concentrations of PD173074 in culture and was subsequently, found to have acquired AKT1 S266L (PMID: 30140389). 30140389
AKT1 positive ovarian clear cell carcinoma predicted - sensitive Cisplatin + Perifosine Preclinical - Cell culture Actionable In a preclinical study, Perifosine (KRX-0401) enhanced the sensitivity of human ovarian clear cell cancer cells with activated Akt1 to Platinol (cisplatin) treatment in culture (PMID: 25519148). 25519148
AKT1 positive ovarian clear cell carcinoma predicted - sensitive Perifosine Preclinical - Cell line xenograft Actionable In a preclinical study, Perifosine (KRX-0401) inhibited Akt1 signaling, inhibited proliferation, and induced apoptosis in human ovarian clear cell cancer cells with activated Akt1 in culture and inhibited tumor growth in cell line xenografts (PMID: 25519148). 25519148
Clinical Trial Phase Therapies Title Recruitment Status