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Profile Name AKT1 amp
Gene Variant Detail

AKT1 amp (no effect)

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 act mut Advanced Solid Tumor no benefit Akt Inhibitor (Pan) 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 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 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 S266L FGFR1 amp lung cancer predicted - sensitive Akt Inhibitor (Pan) 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 wild-type cancer sensitive Akt Inhibitor (Pan) Uprosertib Preclinical Actionable In a preclinical study, GSK2141795 inhibited all isoforms of AKT in human cancer cell lines (PMID: 23795919). 23795919
AKT1 wild-type ovarian cancer predicted - sensitive Akt Inhibitor (Pan) 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 wild-type clear cell renal cell carcinoma sensitive Akt1 Inhibitor 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 W80A breast cancer resistant Akt Inhibitor (Pan) 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 W80A Advanced Solid Tumor resistant Akt Inhibitor (Pan) 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 E17K AKT1 R465C Her2-receptor negative breast cancer sensitive Akt Inhibitor (Pan) Capivasertib + Fulvestrant Case Reports/Case Series Actionable In a clinical study, Capivasertib (AZD5363) treatment in combination with Faslodex (fulvestrant) resulted in a partial response in a Her2-negative breast cancer patient harboring AKT1 E17K and R465C, and inhibited tumor growth in a patient-derived xenograft (PDX) model (PMID: 32220884). 32220884
AKT1 E17K AKT1 R465C Her2-receptor negative breast cancer sensitive Akt Inhibitor (Pan) Capivasertib Preclinical - Pdx Actionable In a preclinical study, Capivasertib (AZD5363) treatment inhibited tumor growth in a patient-derived xenograft (PDX) model of Her2-negative breast cancer harboring AKT1 E17K and R465C (PMID: 32220884). 32220884
AKT1 P68_C77dup breast cancer sensitive Akt Inhibitor (Pan) 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 mutant lung adenocarcinoma no benefit Akt Inhibitor (Pan) Capivasertib Case Reports/Case Series Actionable In a Phase II trial (NLMT), Capivasertib (AZD5363) treatment did not result in a conformed response (0/8) or durable clinical benefit (0/8) in patients with lung adenocarcinoma harboring mutations in PIK3CA, PTEN, or AKT, thus the cohort was closed due to futility (PMID: 32669708, NCT02664935). 32669708
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 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 Akt Inhibitor (Pan) 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 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 mut PIK3CA mut Her2-receptor negative breast cancer sensitive Akt Inhibitor (Pan) Capivasertib Preclinical - Pdx Actionable In a preclinical study, PIK3CA and AKT1 mutations are associated with increased sensitivity to Capivasertib (AZD5363) treatment in patient-derived xenograft (PDX) models of Her2-negative breast cancer compared to PDX models harboring AKT1, PIK3CA, and PTEN mutations (PMID: 32220884). 32220884
AKT1 E17K uterus leiomyosarcoma predicted - sensitive Akt Inhibitor (Pan) Capivasertib Case Reports/Case Series 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 cancer no benefit Akt Inhibitor (Pan) MK2206 Phase II Actionable In a Phase II trial, MK2206 treatment resulted in no objective response in 4 patients with advanced breast cancer harboring AKT1 E17K (PMID: 31277699; NCT01277757). 31277699
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 cancer sensitive Akt Inhibitor (Pan) 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 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 melanoma sensitive Akt Inhibitor (Pan) 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 E17K Advanced Solid Tumor no benefit Akt1 Inhibitor BAY1125976 Phase I Actionable In a Phase I trial, BAY 1125976 treatment demonstrated safety and pharmacological inhibition of Akt signaling, and resulted in stable disease in 33.3% (3/9) of hormone receptor-positive breast cancer patients harboring AKT1 E17K in the dose expansion study, however, AKT1 E17K mutation status did not result in an improved clinical benefit compared to the overall clinical benefit (PMID: 31835495; NCT01915576). 31835495
AKT1 E17K endometrial cancer sensitive Akt Inhibitor (Pan) Miransertib Preclinical - Cell line xenograft Actionable In a preclinical study, an endometrial cell line xenograft model harboring AKT E17K was sensitive to Miransertib (ARQ092), demonstrating inhibition of tumor growth (PMID: 26469692). 26469692
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 granulosa cell tumor sensitive Akt Inhibitor (Pan) 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 triple-receptor negative breast cancer predicted - sensitive Akt Inhibitor (Pan) 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 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 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 triple-receptor negative breast cancer predicted - sensitive Akt Inhibitor (Pan) Capivasertib + Paclitaxel Case Reports/Case Series Actionable In a Phase II trial (PAKT), addition of Capivasertib (AZD5363) to Taxol (paclitaxel) as first-line therapy significantly improved median progression-free survival (9.3 vs 3.7 months, HR=0.30, p=0.01) and reduced risk (66%, HR=0.34, p=0.04) compared to Taxol (paclitaxel) alone in patients with metastatic triple-negative breast cancer harboring activating mutations in AKT1 (E17K, n=1) or PIK3CA (n=17), or inactivating mutations or gene loss in PTEN (n=13) (PMID: 31841354; NCT02423603). 31841354
AKT1 E17K Her2-receptor negative breast cancer 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 Her2-receptor negative breast cancer sensitive Akt Inhibitor (Pan) Capivasertib Preclinical - Pdx Actionable In a preclinical study, Capivasertib (AZD5363) treatment inhibited tumor growth in patient-derived xenograft (PDX) models of Her2-negative breast cancer harboring AKT1 E17K (PMID: 32220884). 32220884
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
AKT1 E17K endometrial cancer predicted - sensitive Akt Inhibitor (Pan) 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 estrogen-receptor positive breast cancer predicted - sensitive Akt Inhibitor (Pan) Capivasertib Phase I Actionable In a Phase I trial, Capivasertib (AZD5363) treatment in patients with ESR1-positive breast cancer harboring AKT1 E17K resulted in an objective response rate of 20% (4/20), with four patients achieving a partial response, stable disease at 24 weeks in 25% (5/20), a duration of response at 6 months or more in 10% (2/20), a clinical benefit rate of 45% at 24 weeks, and a median progression-free survival of 5.4 months (PMID: 32312891; NCT01226316). 32312891
AKT1 E17K lung adenocarcinoma predicted - sensitive Akt Inhibitor (Pan) 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 cervical cancer predicted - sensitive Akt Inhibitor (Pan) 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 breast cancer sensitive Akt Inhibitor (Pan) 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 breast cancer sensitive Akt Inhibitor (Pan) 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 meningothelial meningioma predicted - sensitive Akt Inhibitor (Pan) 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 carcinoma predicted - sensitive Akt Inhibitor (Pan) Miransertib Case Reports/Case Series Actionable In a clinical case study, Miransertib (ARQ092) treatment resulted in complete tumor remission and improved quality of life in a patient harboring AKT1 E17K who had Proteus syndrome and developed ovarian carcinoma, and treatment was ongoing at 22 months (PMID: 31058421). 31058421
AKT1 E17K endometrial adenocarcinoma predicted - sensitive Akt Inhibitor (Pan) Capivasertib Case Reports/Case Series 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 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 parotid gland cancer predicted - sensitive Akt Inhibitor (Pan) Capivasertib Case Reports/Case Series 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 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 FGFR3 Y373C urinary bladder cancer sensitive Akt Inhibitor (Pan) 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 NRAS Q61R bladder carcinoma sensitive Akt1 Inhibitor 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 NRAS G12D prostate cancer sensitive Akt1 Inhibitor 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 positive ovarian clear cell carcinoma predicted - sensitive Akt Inhibitor (Pan) 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 Akt Inhibitor (Pan) 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
AKT1 pos NRAS mut melanoma predicted - resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, one of two NRAS-mutant melanoma cell lines expressing AKT1 demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). 30819666
AKT1 pos NRAS mut melanoma predicted - resistant Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, two of four NRAS-mutant melanoma cell lines expressing AKT1 were resistant to the combination treatment of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 30819666). 30819666
AKT1 pos NRAS mut melanoma predicted - resistant Palbociclib Preclinical - Cell culture Actionable In a preclinical study, two of two NRAS-mutant melanoma cell lines with AKT1 expression demonstrated resistance to treatment with Ibrance (palbociclib) in culture (PMID: 30819666). 30819666
AKT1 pos ARID1A dec exp stomach cancer sensitive GSK690693 Preclinical - Cell culture Actionable In a preclinical study, GSK690693 treatment inhibited phosphorylation of Akt and S6, reduced viability and induced apoptosis in ARID1A knockdown gastric cancer cell lines expressing AKT1 in culture (PMID: 28860825). 28860825
AKT1 pos ARID1A dec exp stomach cancer sensitive Cisplatin + GSK690693 Preclinical - Cell culture Actionable In a preclinical study, GSK690693 in combination with Platinol (cisplatin) resulted in enhanced reduction in cell viability and induced apoptosis in ARID1A knockdown gastric cancer cell lines expressing AKT1 in culture (PMID: 28860825). 28860825
AKT1 pos ARID1A dec exp stomach cancer sensitive Fluorouracil + GSK690693 Preclinical - Cell culture Actionable In a preclinical study, GSK690693 in combination with Adrucil (fluorouracil) resulted in enhanced reduction in cell viability and induced apoptosis in in ARID1A knockdown gastric cancer cell lines expressing AKT1 in culture (PMID: 28860825). 28860825
AKT1 over exp PIK3CA H1047R breast cancer resistant Alpelisib Preclinical - Cell culture Actionable In a preclinical study, Akt1 over expression in breast cancer cells harboring PIK3CA H1047R resulted in resistance to Alpelisib (BYL719) in culture (PMID: 27604488). 27604488
AKT1 over exp PIK3CA E545K breast cancer resistant Pictilisib Preclinical - Cell culture Actionable In a preclinical study, Akt1 over expression in breast cancer cells harboring PIK3CA E545K resulted in resistance to Pictilisib (GDC-0941) in culture (PMID: 27604488). 27604488
AKT1 Q79K ovarian cancer predicted - sensitive Akt Inhibitor (Pan) 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 amp osteosarcoma sensitive Akt Inhibitor (Pan) MK2206 Preclinical - Pdx Actionable In a preclinical study, a patient derived xenograft (PDX) model of osteosarcoma with AKT1 amplification was sensitive to treatment with MK2206, demonstrating reduced tumor growth and increased apoptotic activity (PMID: 30266815). 30266815
AKT1 amp Advanced Solid Tumor predicted - sensitive Akt Inhibitor (Pan) 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
Clinical Trial Phase Therapies Title Recruitment Status
NCT01396408 Phase II Temsirolimus Sunitinib A Phase II Study of Sunitinib or Temsirolimus in Patients With Advanced Rare Tumours Active, not recruiting