Molecular Profile Detail

Profile Name AKT1 E267G
Gene Variant Detail

AKT1 E267G (gain of function - predicted)

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
Unknown unknown Advanced Solid Tumor not applicable Akt Inhibitor (Pan) M2698 Phase I Actionable In a Phase I trial, M2698 (MSC2363318A) demonstrated safety and preliminary efficacy, with 19% (6/32) of advanced solid tumor patients remained on treatment for more than 180 days (Ann Oncol 2017, Vol 28, Suppl 5, Abstract # 370PD; NCT01971515). detail...
Unknown unknown Advanced Solid Tumor not applicable Akt Inhibitor (Pan) M2698 Preclinical Actionable In a preclinical study, MSC2363318A demonstrated sustained inhibition of S6K phosphorylation, and inhibited tumor growth in several human cancer xenograft models of breast, pancreatic, glioblastoma and ovarian cancers (Mol Cancer Ther 2013;12(11 Suppl):A162). detail...
Unknown unknown Advanced Solid Tumor not applicable Akt Inhibitor (Pan) M2698 Phase I Actionable In a Phase I trial, M2698 (MSC2363318A) demonstrated safety and preliminary efficacy in a variety of advanced solid tumor patients (Ann. Oncol. 26 (Suppl 2): ii25-ii27, 2015). detail...
Unknown unknown glioblastoma multiforme not applicable Akt Inhibitor (Pan) LYS6KAKT1 Preclinical Actionable In a preclinical study, LYS6KAKT1 inhibited phosphorylation of p70S6 kinase in mice engrafted with glioblastoma cells (Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B117). detail...
Unknown unknown Advanced Solid Tumor not applicable Akt Inhibitor (Pan) Gemcitabine + LY2780301 Phase Ib/II Actionable In a Phase Ib trial, the combination of LY2780303 and Gemzar (gemcitabine) demonstrated some antitumor activity in patients with advanced solid tumors including 2 patients with a partial response, 28 patients with stable disease, and a four month disease control rate of 22% (PMID: 28750271). 28750271
Unknown unknown Advanced Solid Tumor not applicable Akt Inhibitor (Pan) LY2780301 Phase I Actionable In a Phase I trial, LY2780301 demonstrated safety and preliminary efficacy in patients with a variety of advanced solid tumors (PMID: 25902900). 25902900
Unknown unknown triple-receptor negative breast cancer not applicable Akt Inhibitor (Pan) KP372-1 Preclinical - Cell culture Actionable In a preclinical study, KP372-1 induced complete growth inhibition of triple-receptor negative breast cancer cells in culture (PMID: 27872098). 27872098
Unknown unknown immune system cancer not applicable Akt Inhibitor (Pan) Afuresertib Phase II Actionable In a Phase II trial, treatment with Afuresertib (GSK2110183) in patients with Langerhans cell histiocytosis resulted in an overall response rate of 33% in treatment-naive patients and 28% in patients with refractory disease (PMID: 27804235). 27804235
Unknown unknown ovary epithelial cancer not applicable Akt Inhibitor (Pan) Afuresertib + Carboplatin + Paclitaxel Phase I Actionable In a Phase Ib trial, the combination of Afuresertib (GSK2110183) , Paraplatin (carboplatin), and Taxol (paclitaxel) was well-tolerated and demonstrated preliminary efficacy in patients with platinum-resistant epithelial ovarian cancer, resulting in an overall response rate in the dose-expansion part of the trial (Part II) of 32% (9/28) and a median progression-free survival of 7.1 months (PMID: 30563934; NCT01653912). 30563934
Unknown unknown Advanced Solid Tumor not applicable Akt Inhibitor (Pan) Afuresertib + Trametinib Phase I Actionable In a Phase I trial, the combination of Mekinist (trametinib) and Afuresertib (GSK2110183) was not well-tolerated in patients with advanced solid tumors (PMID: 25417902). 25417902
Unknown unknown triple-receptor negative breast cancer not applicable Akt Inhibitor (Pan) Docetaxel + ONC201 Preclinical - Cell culture Actionable In a preclinical study, the combination of ONC201 and Docefrez (docetaxel) worked synergistically to inhibit viability of triple-negative breast cancer cell lines in culture (PMID: 28424227). 28424227
Unknown unknown mantle cell lymphoma not applicable Akt Inhibitor (Pan) Ibrutinib + ONC201 Preclinical - Patient cell culture Actionable In a preclinical study, the combination of ONC201 and Imbruvica (ibrutinib) induced apoptosis in primary mantle cell lymphoma samples in culture, including Imbruvica (ibrutinib)-resistant samples, with greater efficacy than either agent alone (PMID: 26884599). 26884599
Unknown unknown mantle cell lymphoma not applicable Akt Inhibitor (Pan) ONC201 Preclinical - Patient cell culture Actionable In a preclinical study, ONC201 induced apoptosis and decreased viability of mantle cell lymphoma (MCL) cell lines in culture and demonstrated cytotoxicity in primary MCL samples in culture (PMID: 26884599). 26884599 detail...
Unknown unknown triple-receptor negative breast cancer not applicable Akt Inhibitor (Pan) ONC201 Preclinical - Cell line xenograft Actionable In a preclinical study, ONC201 inhibited viability of several triple-negative breast cancer (TNBC) cell lines in culture, demonstrating variable pro-apototic and anti-proliferative activity, and inhibited tumor growth in TNBC cell line xenograft models (PMID: 28424227). 28424227
Unknown unknown endometrial cancer not applicable Akt Inhibitor (Pan) ONC201 Clinical Study Actionable In a clinical case study, a patient with endometrial cancer demonstrated stable disease for 42 weeks and continued regression of metastatic lesions in the lung when treated with ONC201 (TIC-10) (PMID: 28331050). 28331050
Unknown unknown breast cancer not applicable Akt Inhibitor (Pan) ONC201 Preclinical - Cell line xenograft Actionable In a preclinical study, ONC201 inhibited viability of several breast cancer cell lines in culture (including triple-negative breast cancer (TNBC) and non-TNBC cell lines), with some cell lines demonstrating increased apoptosis, and inhibited tumor growth in TNBC cell line xenograft models (PMID: 28424227). 28424227
Unknown unknown prostate cancer not applicable Akt Inhibitor (Pan) ONC201 Clinical Study Actionable In a clinical case study, a prostate cancer patient demonstrated tumor regression in the primary tumor and metastatic lesions when treated with ONC201 (TIC-10) (PMID: 28331050). 28331050
Unknown unknown Advanced Solid Tumor not applicable Akt Inhibitor (Pan) ONC201 Phase I Actionable In a Phase I trial, ONC201 treatment resulted in stable disease in 80% (8/10) of patients with advanced solid tumors (J Clin Oncol 34, 2016 (suppl; abstr 2514)). detail...
Unknown unknown Advanced Solid Tumor not applicable Akt Inhibitor (Pan) ONC201 Preclinical - Cell line xenograft Actionable In a preclinical study, ONC-201 (TIC-10) induced apoptosis and tumor regression in a variety of cell line xenograft models, including colon, breast, and brain cancer (PMID: 23390247). 23390247
Unknown unknown endometrial clear cell adenocarcinoma not applicable Akt Inhibitor (Pan) ONC201 Clinical Study Actionable In a clinical case study, a patient with clear cell endometrial cancer treated with ONC201 (TIC-10) demonstrated some reduction in lesion size (>30%), but also developed new lesions (PMID: 28331050). 28331050
Unknown unknown acute myeloid leukemia not applicable Akt Inhibitor (Pan) ONC201 Preclinical - Pdx & cell culture Actionable In a preclinical study, ONC201 treatment induced ATF4 expression and apoptosis in acute myeloid leukemia (AML) cell lines in culture, independent of Tp53 status, and was toxic to AML primary samples in culture, resulting in decreased engraftment in xenograft models (PMID: 26884599). 26884599
Unknown unknown prostate adenocarcinoma not applicable Akt Inhibitor (Pan) ONC201 Clinical Study Actionable In a clinical case study, a prostate adenocarcinoma patient demonstrated extended stable disease for 27 weeks when treated with ONC201 (TIC-10) (PMID: 28331050). 28331050
Unknown unknown multiple myeloma not applicable Akt Inhibitor (Pan) ONC201 Preclinical - Cell culture Actionable In a preclinical study, a Velcade (bortezomib)-resistant multiple myeloma cell line demonstrated sensitivity to ONC201 in culture (PMID: 26884599). 26884599
Unknown unknown triple-receptor negative breast cancer not applicable Akt Inhibitor (Pan) ONC201 + Paclitaxel Preclinical - Cell culture Actionable In a preclinical study, the combination of ONC201 and Taxol (paclitaxel) worked synergistically to inhibit viability of triple-negative breast cancer cell lines in culture (PMID: 28424227). 28424227
Unknown unknown acute myeloid leukemia not applicable Akt Inhibitor (Pan) ONC201 + Venetoclax Preclinical - Cell culture Actionable In a preclinical study, the combination of ONC201 and Venclexta (venetoclax) demonstrated synergy in acute myeloid leukemia cell lines in culture, resulting in increased induction of apoptosis (PMID: 26884599). 26884599
Unknown unknown mantle cell lymphoma not applicable Akt Inhibitor (Pan) ONC201 + Venetoclax Preclinical - Cell culture Actionable In a preclinical study, the combination of ONC201and Venclexta (venetoclax) demonstrated synergy in a mantle cell lymphoma cell line in culture, resulting in increased induction of apoptosis (PMID: 26884599). 26884599
Unknown unknown ovarian cancer not applicable Akt Inhibitor (Pan) ABT-737 + MK2206 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of MK2206 and Mekinist (trametinib) enhanced the sensitivity of ovarian cancer cells to ABT-737 in culture, resulting in decreased cell viability (PMID: 27980105). 27980105
Unknown unknown chronic lymphocytic leukemia not applicable Akt Inhibitor (Pan) Bendamustine + MK2206 + Rituximab Phase Ib/II Actionable In a Phase I trial, MK2206 in combination with Bendamustine and Rituximab resulted in an overall response rate of 92% (12/13), with a median progression free survival of 16 months and a treatment free survival of 24 months in patients with relapsed or refractory chronic lymphocytic leukemia (PMID: 28402581). 28402581
Unknown unknown Advanced Solid Tumor not applicable Akt Inhibitor (Pan) Lapatinib + MK2206 Phase I Actionable In a Phase I trial, Tykerb (lapatinib) and MK2206 combination treatment resulted in stable disease for more than 4 months in 9% (2/23) of patients with advanced solid tumors (PMID: 27026198). 27026198
Unknown unknown gastric adenocarcinoma not applicable Akt Inhibitor (Pan) MK2206 Phase II Actionable In a Phase II trial, MK2206 demonstrated safety, but did not meet study endpoint of median overall survival of 6.5 months, however gastric adenocarcinoma patients were not stratified according to somatic profiles (PMID: 25827820). 25827820
Unknown unknown Advanced Solid Tumor not applicable Akt Inhibitor (Pan) MK2206 Phase I Actionable In a Phase I clinical trial, MK2206 demonstrated safety and preliminary efficacy in patients with advanced solid tumors (PMID: 22025163). 22025163
Unknown unknown renal cell carcinoma no benefit Akt Inhibitor (Pan) MK2206 Phase II Actionable In a Phase II trial, MK2206 treatment resulted in shorter progression free survival compared to Afinitor (everolimus) (3.68 vs 5.98 months) in patients with renal cell carcinoma (PMID: 28049139). 28049139
Unknown unknown Advanced Solid Tumor not applicable Akt Inhibitor (Pan) MK2206 + Paclitaxel Phase Ib/II Actionable In a Phase Ib clinical trial, the combination of MK2206 and Taxol (paclitaxel) was well tolerated and demonstrated preliminary efficacy in patients with advanced solid tumors, with partial response in 24% (5/21) and stable disease in 43% (9/21) of patients (PMID: 25688104) 25688104
Unknown unknown pancreatic adenocarcinoma no benefit Akt Inhibitor (Pan) MK2206 + Selumetinib Phase II Actionable In a Phase II trial, the combination of Selumetinib (AZD6244) and MK2206 did not result in improved median overall survival compared to mFOLFOX therapy (3.9 mo vs. 6.7 mo) or improved median progression-free survival (1.9 mo vs 2.0 mo) in patients with pancreatic adenocarcinoma (PMID: 27978579). 27978579
Unknown unknown ovarian cancer not applicable Akt Inhibitor (Pan) Cisplatin + Uprosertib Preclinical - Cell line xenograft Actionable In a preclinical study, the addition of GSK2141795 re-sensitized platinum-resistant ovarian cancer cell lines to Platinol (cisplatin) in culture, and treatment with the combination of GSK2141795 and Platinol (cisplatin) resulted in increased tumor growth inhibition in ovarian cancer xenograft models compared to Platinol (cisplatin) alone (PMID: 26497682). 26497682
Unknown unknown Advanced Solid Tumor not applicable Akt Inhibitor (Pan) Trametinib + Uprosertib Phase I Actionable In a Phase I trial, the combination of Trametinib (GSK1120212) and Uprosertib (GSK2141795) demonstrated safety and preliminary efficacy in patients with advanced solid tumors (J Clin Oncol (Meeting Abstracts) 2011 29: 3085). detail...
Unknown unknown Advanced Solid Tumor not applicable Akt Inhibitor (Pan) ARQ 751 Preclinical - Cell culture Actionable In a preclinical study, treatment with ARQ 751 resulted in anti-proliferative activity in a variety of cancer cell lines in culture (PMID: 26469692). 26469692
Unknown unknown diffuse large B-cell lymphoma not applicable Akt Inhibitor (Pan) AT-7867 Preclinical - Cell culture Actionable In a preclinical study, AT-7867 inhibited the growth of diffuse large B-cell lymphoma cell lines in culture (PMID: 26824321). 26824321
Unknown unknown acute myeloid leukemia not applicable Akt Inhibitor (Pan) AZD1897 + Capivasertib Preclinical Actionable In a preclinical study, acute myeloid leukemia cells treated with the combination of AZD1897 and AZD5363 produced a synergistic effect, resulting in decreased cell survival (PMID: 24975213). 24975213
Unknown unknown prostate cancer not applicable Akt Inhibitor (Pan) Capivasertib + Docetaxel + Prednisone Phase I Actionable In a Phase I trial, AZZD5363 in combination with Taxotere (docetaxel) and Prednisone resulted in more than 50% PSA reduction at 12 weeks in 70% (7/10) of patients with metastatic castration resistant prostate cancer (PMID: 28144789; NCT02121639). 28144789
Unknown unknown endometrial cancer not applicable Akt Inhibitor (Pan) Capivasertib + Olaparib Phase I Actionable In a Phase I trial, the combination of AZD5363 and Lynparza (olaparib) was well-tolerated and demonstrated preliminary activity in patients with endometrial, ovarian, or triple-negative breast cancer (TNBC), with an overall response rate of 24% (7/30; all partial responses, 1 ovarian, 4 endometrial, and 2 TNBC) and stable disease for greater than 4 months in 6 additional patients, and a response rate of 50% (4/8) in endometrial cancer patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #391P; NCT02208375). detail...
Unknown unknown ovarian cancer not applicable Akt Inhibitor (Pan) Capivasertib + Olaparib Phase I Actionable In a Phase I trial, the combination of AZD5363 and Lynparza (olaparib) was well-tolerated and demonstrated preliminary activity in patients with endometrial, ovarian, or triple-negative breast cancer (TNBC), with an overall response rate of 24% (7/30; all partial responses, 1 ovarian, 4 endometrial, and 2 TNBC) and stable disease for greater than 4 months in 6 additional patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #391P; NCT02208375). detail...
Unknown unknown triple-receptor negative breast cancer not applicable Akt Inhibitor (Pan) Capivasertib + Olaparib Phase I Actionable In a Phase I trial, the combination of AZD5363 and Lynparza (olaparib) was well-tolerated and demonstrated preliminary activity in patients with endometrial, ovarian, or triple-negative breast cancer (TNBC), with an overall response rate of 24% (7/30; all partial responses, 1 ovarian, 4 endometrial, and 2 TNBC) and stable disease for greater than 4 months in 6 additional patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #391P; NCT02208375). detail...
Unknown unknown Her2-receptor negative breast cancer not applicable Akt Inhibitor (Pan) Capivasertib + Paclitaxel Phase II Actionable In a Phase II trial, addition of AZD5363 to Taxol (paclitaxel) did not improve progression free survival compared to placebo (10.9 vs 8.4 months) in patients with Esr1-positive, Erbb2 (Her2)-negative breast cancer (Ann Oncol 2017, Vol 28, Suppl 5, Abstract # 241PD; NCT01625286). detail...
Unknown unknown triple-receptor negative breast cancer not applicable Akt Inhibitor (Pan) 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 (5.9 vs 4.2 months, HR=0.75, p=0.06) and median overall survival (19.1 vs 12.6 months, HR=0.64, p=0.02) compared to placebo in patients with metastatic triple-negative breast cancer (J Clin Oncol 36, no. 15_suppl (May 20 2018) 1007-1007; NCT02423603). detail...
Unknown unknown Advanced Solid Tumor not applicable Akt Inhibitor (Pan) Cobimetinib + Ipatasertib Phase I Actionable In a Phase I clinical trial Ipatasertib (GDC-0068), in combination with the Mek inhibitor Cobimetinib (GDC-0973) demonstrated safety and preliminary efficacy in patients with advanced solid tumors (Cancer Res, October 1, 2014 74; CT328). detail...
Unknown unknown Advanced Solid Tumor not applicable Akt Inhibitor (Pan) Ipatasertib Preclinical - Cell line xenograft Actionable In a preclinical study, Ipatasertib (GDC-0068) demonstrated activity against tumor growth in cell line xenograft models of solid tumors (PMID: 24141624). 24141624
Unknown unknown Advanced Solid Tumor not applicable Akt Inhibitor (Pan) Ipatasertib Phase I Actionable In a Phase I trial, Ipatasertib (GDC-0068) resulted in antitumor activity in 30% (16/52) of patients with advanced solid tumors, primarily demonstrating stable disease (PMID: 27872130). 27872130
Unknown unknown triple-receptor negative breast cancer not applicable 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 patients with triple-receptor negative breast cancer (PMID: 28800861; NCT02162719). 28800861 detail...
Unknown unknown Advanced Solid Tumor not applicable Akt Inhibitor (Pan) ARQ092 Phase I Actionable In a Phase I trial, ARQ092 demonstrated safety and is currently being tested for efficacy in clinical trials in patients with advanced solid tumors (American Association for Cancer Research. April 6-10, 2013. Abstract #LB-197). detail...
Unknown unknown lung cancer not applicable Akt Inhibitor (Pan) ABT-737 + Perifosine Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of ABT-737 and perifosine worked synergistically to induce apoptosis and inhibit growth of lung cancer cell lines and primary lung cancer cells in culture, and to inhibit tumor growth in a lung cancer cell line xenograft model (PMID: 27073162). 27073162
Unknown unknown Advanced Solid Tumor not applicable Akt Inhibitor (Pan) Perifosine Phase I Actionable In a Phase I trial, Perifosine demonstrated safety and preliminary efficacy in patients with a variety of advanced solid tumors (PMID: 25183650). 25183650
Unknown unknown stomach cancer not applicable Akt1 Inhibitor RX-0201 Preclinical Actionable In a preclinical study, RX-0201 prevented cell proliferation of stomach cancer cells (JASCO Annual Meeting Proceedings Vol 24, No 18S (June 20 Supplement), 2006: 13102). detail...
Unknown unknown melanoma not applicable Akt1 Inhibitor A-674563 Preclinical - Cell line xenograft Actionable In a preclinical study, a melanoma cell line demonstrated sensitivity to A-674563, resulting in apoptotic activity and inhibition of Akt1 activity in culture, and inhibition of tumor growth in xenograft models (PMID: 26970307). 26970307
Unknown unknown prostate cancer not applicable Akt1 Inhibitor NSC156529 Preclinical - Cell line xenograft Actionable In a preclinical study, NSC156529 inhibited growth of human prostate cancer cell lines in culture, induced expression of differentiation markers and inhibited tumor growth in cell line xenograft models (PMID: 26294745). 26294745
Unknown unknown Advanced Solid Tumor not applicable Akt1 Inhibitor NSC156529 Preclinical Actionable In a preclinical study, NSC156529 inhibited growth of transformed human cell lines in culture (PMID: 26294745). 26294745
Unknown unknown hepatocellular carcinoma not applicable Akt1 Inhibitor NSC156529 Preclinical Actionable In a preclinical study, NSC156529 inhibited growth of human hepatocellular carcinoma cell lines in culture (PMID: 26294745). 26294745
Clinical Trial Phase Therapies Title Recruitment Status