^
    23d
    Robust anti-myeloma effect of TAS0612, an RSK/AKT/S6K inhibitor, with venetoclax regardless of cytogenetic abnormalities. (PubMed, Leukemia)
    Moreover, the combination of TAS0612 with venetoclax (VEN) showed the synergy in inducing apoptosis in HMCLs irrespective of the t(11;14) translocation status. TAS0612 alone and combined with VEN are new potent candidate therapeutic strategies for MM, regardless of cytogenetic/genetic profiles, facilitating its future clinical development.
    Journal
    |
    RPS6KA3 (Ribosomal Protein S6 Kinase A3) • PDPK1 (3-Phosphoinositide dependent protein kinase 1)
    |
    Chr t(11;14)
    |
    Venclexta (venetoclax) • TAS0612
    9ms
    A Study of TAS0612 in Participants With Advanced or Metastatic Solid Tumor Cancer (clinicaltrials.gov)
    P1, N=100, Recruiting, Taiho Oncology, Inc. | N=242 --> 100 | Trial completion date: Jun 2024 --> Jul 2027 | Trial primary completion date: Oct 2023 --> Jul 2024
    Enrollment change • Trial completion date • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • PTEN (Phosphatase and tensin homolog) • NF1 (Neurofibromin 1)
    |
    KRAS mutation • HR positive • KRAS G12C • HER-2 negative • KRAS G12D • NF1 mutation • KRAS G12 • HR positive + HER-2 negative
    |
    TAS0612
    1year
    TAS0612, a novel RSK, AKT, and S6K inhibitor, exhibits antitumor effects in preclinical tumor models. (PubMed, Mol Cancer Ther)
    Additionally, TAS0612 demonstrated the persistence of blockade of downstream growth and anti-apoptotic signals, despite activation of upstream effectors in the signaling pathway and FoxO-dependent re-expression of HER3. In conclusion, TAS0612 with RSK/AKT/S6K inhibitory activity may provide a novel therapeutic strategy for cancer patients to improve clinical responses and overcome resistance mechanisms.
    Preclinical • Journal
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PTEN (Phosphatase and tensin homolog) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    KRAS mutation • BRAF mutation • ERBB3 expression
    |
    TAS0612
    1year
    Triple targeting of RSK, AKT, and S6K as pivotal downstream effectors of PDPK1 by TAS0612 in B-cell lymphomas. (PubMed, Cancer Sci)
    At the molecular level, TAS0612 caused significant downregulation of MYC and mTOR target genes while inducing the tumor suppressor TP53INP1 protein in these cell lines. These results prove that the simultaneous blockade of RSK2, AKT, and S6K, which are the pivotal downstream substrates of PDPK1, is a novel therapeutic target for the various disease subtypes of BCLs and line up TAS0612 as an attractive candidate agent for BCLs for future clinical development.
    Journal
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PLK1 (Polo Like Kinase 1) • RPS6KA3 (Ribosomal Protein S6 Kinase A3) • PDPK1 (3-Phosphoinositide dependent protein kinase 1) • TP53INP1 (Tumor Protein P53 Inducible Nuclear Protein 1)
    |
    TAS0612
    almost3years
    A Study of TAS0612 in Participants With Advanced or Metastatic Solid Tumor Cancer (clinicaltrials.gov)
    P1, N=242, Recruiting, Taiho Oncology, Inc. | Trial completion date: Dec 2023 --> Jun 2024 | Trial primary completion date: Jun 2023 --> Oct 2023
    Clinical • Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • PTEN (Phosphatase and tensin homolog) • NF1 (Neurofibromin 1)
    |
    KRAS mutation • HR positive • KRAS G12C • HER-2 negative • KRAS G12D • NF1 mutation • KRAS G12 • HR positive + HER-2 negative
    |
    TAS0612
    almost4years
    A Study of TAS0612 in Participants With Advanced or Metastatic Solid Tumor Cancer (clinicaltrials.gov)
    P1, N=200, Recruiting, Taiho Oncology, Inc. | Not yet recruiting --> Recruiting
    Clinical • Enrollment open
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • PTEN (Phosphatase and tensin homolog) • NF1 (Neurofibromin 1)
    |
    KRAS mutation • HR positive • KRAS G12C • HER-2 negative • KRAS G12D • NF1 mutation • KRAS G12 • HR positive + HER-2 negative
    |
    TAS0612
    4years
    A Study of TAS0612 in Participants With Advanced or Metastatic Solid Tumor Cancer (clinicaltrials.gov)
    P1, N=200, Not yet recruiting, Taiho Oncology, Inc.
    Clinical • New P1 trial
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • PTEN (Phosphatase and tensin homolog) • NF1 (Neurofibromin 1)
    |
    KRAS mutation • HR positive • KRAS G12C • HER-2 negative • KRAS G12D • NF1 mutation • KRAS G12 • HR positive + HER-2 negative
    |
    TAS0612
    almost5years
    Targeting phosphorylation of Y-box binding protein YBX1 by TAS0612 and everolimus in overcoming antiestrogen resistance. (PubMed, Mol Cancer Ther)
    Here we found that increased expression of pYBX1 was accompanied by acquired resistance to antiestrogens, fulvestrant and tamoxifen. TAS0612 also demonstrated antitumor effect against triple-negative breast cancer in vivo. Taken together our findings suggest that pYBX1 represents a potential therapeutic target for treatment of antiestrogen resistant and progressive breast cancer.
    Journal
    |
    YBX1 (Y-Box Binding Protein 1)
    |
    everolimus • tamoxifen • fulvestrant • TAS0612