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  • ||||||||||  Erleada (apalutamide) / J&J
    Journal; Preclinical:  Context-Specific Efficacy of Apalutamide Therapy in Preclinical Models of Pten-Deficient Prostate Cancer. (Pubmed Central) -  Jun 25, 2021   
    Upregulation of signal transducer and activator of transcription 3 (STAT3) and proviral insertion in murine-1 (PIM-1) were associated with combined apalutamide/GSK690693. Our findings show that apalutamide can attenuate Pten-deficient PCa in a context-specific manner and provides data that can be used to further study and, possibly, develop additional combinations with apalutamide.
  • ||||||||||  unesbulin (PTC596) / PTC Therap, UNC1999 / University of North Carolina-Chapel Hill, TAS-117 / Otsuka
    Journal:  Novel epigenetic therapies for multiple myeloma (Pubmed Central) -  May 10, 2021   
    Finally, our mouse model with concurrent loss of the histone demethylase Utx and the activating mutation of Braf V600E in post germinal center B cells demonstrates mature B-cell malignancies including plasma cell neoplasms. Our ongoing analyses will reveal the pathogenesis of MM induced by somatic mutations, and this model is a useful tool for the development of novel molecular-targeted therapies for MM patients.
  • ||||||||||  morphine sulphate / Generic mfg.
    Journal:  New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB. (Pubmed Central) -  May 7, 2021   
    In addition, C5a inhibitor PMX enhanced the MP-induced downregulation of NF-κB, while NF-κB inhibitor QNZ had no effect on C5a, indicating that the C5a/NF-κB signaling pathway is involved in MP-induced cardioprotection. HSP90 is critical for MP-mediated cardioprotection possibly by promoting the phosphorylation of Akt and inhibiting the activation of C5a and NF-κB signaling and the subsequent myocardial inflammation, ultimately attenuating the infarct size and cardiomyocyte apoptosis.
  • ||||||||||  MK-2206 / Merck (MSD), ipatasertib (GDC-0068) / Roche, afuresertib (LAE002) / Laekna Therap, capivasertib (AZD5363) / Otsuka, AstraZeneca, GSK690693 / GSK
    Journal:  Chemical Phosphoproteomics Sheds New Light on the Targets and Modes of Action of AKT Inhibitors. (Pubmed Central) -  Mar 23, 2021   
    These included CEP170 and FAM83H, suggesting a regulatory function of AKT in mitosis and cytoskeleton organization. In addition, a specific phosphorylation pattern on the ULK1-FIP200-ATG13-VAPB complex was found to determine the active state of ULK1, leading to elevated autophagy in response to AKT inhibition.
  • ||||||||||  TAS-117 / Otsuka
    Biomarker; Enrollment change; Pan tumor; Trial completion; Trial completion date:  K-BASKET, TAS-117, PI3K/AKT Gene Aberration (clinicaltrials.gov) -  Jun 30, 2020   
    P2,  N=13, Completed, 
    Recruiting -> Completed | N=30 -> 13 | Trial completion date: Dec 2020 -> Dec 2019
  • ||||||||||  futibatinib (TAS 120) / Otsuka, TAS-117 / Otsuka
    [VIRTUAL] Synergistic antitumor activity of futibatinib, an FGFR1-4 inhibitor, and TAS-117, a selective AKT inhibitor, in FGFR-deregulated cancer models (AACR-II 2020) -  May 16, 2020 - Abstract #661/8; Author: Junya Iwasaki; Takuya Kuramoto; Toshiharu Komori; Hitoshi Saito; Hiroshi Hirai; Presentation Time: June 22, 2020; 09:00-18:00   
    Treatment with 3 different futibatinib plus TAS-117 combination dosing regimens resulted in marked reductions in RTVs on Day 15 (2.16, 0.53, and 0.22). Our findings suggest that futibatinib plus TAS-117 has synergistic antitumor effects in FGFR-aberrant tumors. A phase 1/2 study of this combination in advanced solid tumors (JapicCTI-194864) is ongoing.
  • ||||||||||  GSK690693 / GSK
    Journal:  MTHFD2 facilitates breast cancer cell proliferation via the AKT signaling pathway. (Pubmed Central) -  Jan 19, 2020   
    Taken together, the findings from the present study suggested that MTHFD2 may serve a protumor role in the malignancy of breast cancer by activating the AKT signaling pathway. These results provide an alternative theoretical foundation that could help the development of MTHFD2-targeted breast cancer treatment.
  • ||||||||||  GSK2816126 / GSK, TAS-117 / Otsuka
    Akt Inhibition Differently Controls PRC2 Components and Synergizes with Dual EZH2/1 Inhibitor in the Treatment of Multiple Myeloma (ASH 2019) -  Nov 7, 2019 - Abstract #4400; Author: Mohamed Rizk, BSc, MSc1; Ola Rizq, MD, PhD2; Motohiko Oshima, PhD1; Yaeko Nakajima-Takagi, PhD1; Shuhei Koide, PhD1; Atsunori Saraya3; Yusuke Isshiki, MD, PhD4; Tetsuhiro Chiba, MD, PhD5; Satoshi Yamazaki, PhD6; Anqi Ma, PhD7; Jian Jin, PhD7; Atsushi Iwama, MD, PhD1; Naoya Mimura, MD, PhD8; Presentation Time: December 09, 2019; 18:00-20:00   
    In conclusion, the present results defined novel signaling-epigenetic crosstalk between PI3K/Akt pathway and PRC2 components, EZH2 and EZH1, and demonstrated that Akt inhibition can differently modulates EZH2 and EZH1 levels via Akt downstream effectors, E2F1 and FOXO3, respectively. Therefore, targeting both EZH2 and EZH1 in addition to Akt inhibition may be a promising rationale to eradicate MM, leading to significant advances in treatment.
  • ||||||||||  TAS-117 / Otsuka
    First-in-human phase I study of TAS-117, an allosteric AKT inhibitor, in patients with advanced solid tumours (ESMO 2019) -  Sep 11, 2019 - Abstract #456P; Author: M. Yunokawa 1; S. Takahashi 2; D. Aoki 3; K. Yonemori 4; H. Hara 5; K. Hasegawa 6; K. Takehara 7; K. Harano 8; H. Nomura 9; E. Noguchi 4; K. Horie 5; A. Ogasawara 6; S. Okame 7; T. Doi 10; Presentation Time: September 28, 2019; 12:00-13:00   
    Legal entity responsible for the study: Taiho Pharmaceutical Co., Ltd. Funding: Has not received any funding.
  • ||||||||||  pamufetinib (TAS-115) / Otsuka, TAS-117 / Otsuka
    The K-BASKET trial: A prospective phase II biomarker-driven multiple basket trial in Korean solid cancer patients (ESMO 2019) -  Sep 11, 2019 - Abstract #172TiP; Author: S. Kim 1; H.J. Choi 2; M.H. Kim 3; M. Jung 4; S.-H. Beom 5; G.M. Kim 1; S.J. Shin 6; H.C. Chung 2; Presentation Time: September 30, 2019; 12:00-13:00   
    Legal entity responsible for the study: Yonsei University. Funding: National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (HA16C0018).
  • ||||||||||  GSK2816126 / GSK, TAS-117 / Otsuka
    Journal:  Akt Inhibition Synergizes with PRC2 Inhibition in the Treatment of Multiple Myeloma. (Pubmed Central) -  Aug 28, 2019   
    Moreover, FOXO3 knockdown repressed EZH1 expression. Collectively, the present results unravel some molecular interactions between Akt signaling and epigenetic modulators, which emphasize the benefits of targeting PRC2 full activity and the Akt pathway as a therapeutic option for multiple myeloma.
  • ||||||||||  doxorubicin hydrochloride / Generic mfg.
    Journal:  Chemosensitivity and chemoresistance in endometriosis - differences for ectopic versus eutopic cells. (Pubmed Central) -  Apr 28, 2019   
    Overall, the results confirm evidence of large-scale metabolic reprogramming in endometriotic cells, which underlies the observed differences in sensitivity towards toxins. The enhanced efficiency of doxorubicin interfering with redox equilibria and/or DNA repair mechanisms pinpoints key players that can be potentially used to selectively target ectopic lesions in endometriosis.
  • ||||||||||  ispinesib (SB-715992) / Cytokinetics, KW 2478 / Kyowa Kirin, AT9283 / Otsuka, GSK690693 / GSK, colchicine / Generic mfg., AT7519 / Novartis, Otsuka, gedatolisib (PF-05212384) / Curie Institute, Pfizer
    Journal:  A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. (Pubmed Central) -  Jan 28, 2019   
    Of the 10,804 compounds screened, a total of 90 substrates were identified of which 55 were novel. P-gp expression may adversely affect the oral bioavailability or brain penetration of these compounds.
  • ||||||||||  vistusertib (AZD2014) / AstraZeneca, GSK690693 / GSK, Zarnestra (tipifarnib) / Kura Oncology
    Journal:  Comparative toxicity evaluation of targeted anticancer therapeutics in embryonic zebrafish and sea urchin models. (Pubmed Central) -  Dec 28, 2018   
    AZD2014 also caused the least prominent effects on sea urchin embryo development compared to other inhibitors. Significant toxicity of AZD2014 in human cancer cells, its capacity to sensitize resistant cancers, lower antiproliferative activity against human normal cell lines and fast proliferating embryonic cells could make this agent a promising candidate for anticancer therapy.
  • ||||||||||  GSK690693 / GSK
    Journal:  SKA3 promotes cell proliferation and migration in cervical cancer by activating the PI3K/Akt signaling pathway. (Pubmed Central) -  Sep 6, 2018   
    Additionally, the use of an Akt inhibitor (GSK690693) significantly reversed the cell proliferation capacity induced by SKA3 overexpression in HeLa cells. We suggest that SKA3 overexpression contributes to CC cell growth and migration by promoting cell cycle progression and activating the PI3K-Akt signaling pathway, which may provide potential novel therapeutic targets for CC treatment.
  • ||||||||||  TAS-117 / Otsuka
    Biomarker; Enrollment open; Pan tumor:  K-BASKET, TAS-117, PI3K/AKT Gene Aberration (clinicaltrials.gov) -  Jun 25, 2018   
    P2,  N=13, Recruiting, 
    Not yet recruiting -> Recruiting
  • ||||||||||  ZSTK474 / Zenyaku Kogyo, GSK690693 / GSK
    What happens when astrocytes talk to neurons? A proteomic PI3K interactome study (ARVO 2018) -  May 8, 2018 - Abstract #1486 - C0228; Author: Samih Alqawlaq1,2, izhar Livne-bar1,2, Darren Chan1,2, Jeremy M. Sivak1,2; Presentation Time: April 30, 2018; 08:15-10:00   
    PI3K interactome analysis identified a number of upstream and downstream targets activated in neurons following ACM exposure.Conclusions Our findings demonstrate that ACM neuroprotection is mediated through the PI3K pathway. As several inducers and down-stream targets in the PI3K were identified, these findings will enable additional exploration of mechanisms to promote astrocyte secreted neuroprotective signals.
  • ||||||||||  GSK690693 / GSK
    Journal:  Profiling and targeting of cellular mitochondrial bioenergetics: inhibition of human gastric cancer cell growth by carnosine. (Pubmed Central) -  Apr 2, 2018   
    In SGC-7901 cell xenograft nude mice, administration of carnosine (250 mg kg/d, ip, for 3 weeks) significantly inhibited the tumor growth and decreased the expression of mitochondrial PHB-1 in tumor tissue. Taken together, these results suggest that carnosine may act on multiple mitochondrial proteins to down-regulate mitochondrial bioenergetics and then to inhibit the growth and proliferation of SGC-7901 and BGC-823 cells.
  • ||||||||||  Erleada (apalutamide) / J&J
    Apalutamide (ARN-509) demonstrates therapeutic efficacy in genetically engineered mouse models of Pten-deficient prostate cancer (AACR 2018) -  Mar 16, 2018 - Abstract #3737 / 7; Author: Marco A. De Velasco1, Masahiro Nozawa1, Yurie Kura1, Naomi Ando1, Noriko Sato1, Kazuhiro Yoshimura1, Kazuko Sakai1, Kazuhiro Yoshikawa2, Kazuto Nishio1, Hirotsugu Uemura1. 1Kindai University Faculty of Medicine, Osaka-Sayama, Japan; 2Aichi Medical University, Japan; Presentation Time: April 17, 2018; 08:00-12:00   
    Studies to further evaluate the therapeutic benefit of apalutamide plus PI3K/AKT signal blockade in models of advanced prostate cancer are underway. In conclusion, our findings show that apalutamide is active in GEM-PCa models and support further investigation for developing rational treatment combinations for the management of advanced prostate cancer.
  • ||||||||||  GSK690693 / GSK
    Biomarker; Journal:  AKT inhibition is an effective treatment strategy in ARID1A-deficient gastric cancer cells. (Pubmed Central) -  Sep 2, 2017   
    Loss of ARID1A expression is a surrogate marker for the activation of the AKT signaling pathway and is also a reliable biomarker to predict the response for the AKT inhibitor. We anticipate that appropriate patient selection based on ARID1A expression in the tumor tissue will increase the drug sensitivity for the AKT inhibition and improve the clinical outcome.
  • ||||||||||  MK-2206 / Merck (MSD), GSK690693 / GSK
    Journal:  Expanding primary cells from mucoepidermoid and other salivary gland neoplasms for genetic and chemosensitivity testing. (Pubmed Central) -  Aug 8, 2017   
    Procedures employed here illustrate an approach for reproducibly obtaining material for pathophysiological studies of salivary gland neoplasms, and other less common epithelial cancer types, that can be executed without compromising pathological examination of patient specimens. The approach permits combined genetic and cell-based physiological and therapeutic investigations in addition to more traditional pathologic studies, and can be used to build sustainable bio-banks for future inquiries.This article has an associated First Person interview with the first author of the paper.