Anti-tumor effect of AZD8055 against neuroblastoma cells in vitro and in vivo

Xu, Dongqing; Toyoda, Hidemi; Yuan, Xiaojun; Lei, Qi; Chelakkot, Vipin Shankar; Morimoto, Mari; Hanaki, Ryo; Kihira, Kentarou; Hori, Hiroki; Komada, Yoshihiro; Hirayama, Masahiro

doi:10.1016/j.yexcr.2018.02.032

Cited by 24 publications

(27 citation statements)

References 36 publications

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“…The pattern of IGF-1 receptor/PI3K/Akt/mTOR pathway-mediated proliferation is an important determinant of the response to IGF-1 receptor antagonistic therapy in human NB [10]. Furthermore, our results highlight the potential of IGF-1 receptor/PI3K/Akt/mTOR signaling pathway as a promising target for NB treatment [10][11][12][13].…”

Section: Introductionmentioning

confidence: 55%

“…The PI3K/Akt/ mTOR pathway can be activated by transmembrane tyrosine kinase growth factor receptors, such as IGF-1 receptor, fibroblast growth factor receptors, ErbB family receptors, and others [40,41]. Both mTOR S2448 and mTOR S2481 were extensively phosphorylated in NB cell lines [13]. Cell proliferation of NB cell lines was inhibited by AZD8055, a potent dual mTORC1-mTORC2 inhibitor [13].…”

Section: Inhibition Of Nb Cell Proliferation By Mtor Inhibitormentioning

confidence: 99%

“…Both mTOR S2448 and mTOR S2481 were extensively phosphorylated in NB cell lines [13]. Cell proliferation of NB cell lines was inhibited by AZD8055, a potent dual mTORC1-mTORC2 inhibitor [13]. According to the IC 50 , the NB cell lines were divided into two groups, sensitive to AZD8055 group (IC 50 < 0.5 μM) and insensitive to AZD8055 group (IC 50 > 0.5 μM) [13].…”

Section: Inhibition Of Nb Cell Proliferation By Mtor Inhibitormentioning

confidence: 99%

“…Cell proliferation of NB cell lines was inhibited by AZD8055, a potent dual mTORC1-mTORC2 inhibitor [13]. According to the IC 50 , the NB cell lines were divided into two groups, sensitive to AZD8055 group (IC 50 < 0.5 μM) and insensitive to AZD8055 group (IC 50 > 0.5 μM) [13]. We also found that insensitive group showed lower mTOR (p < 0.001) expression and lower activity of mTOR complex 1 (p = 0.013) and mTOR complex 2 (p = 0.023) [13].…”

Section: Inhibition Of Nb Cell Proliferation By Mtor Inhibitormentioning

confidence: 99%

“…According to the IC 50 , the NB cell lines were divided into two groups, sensitive to AZD8055 group (IC 50 < 0.5 μM) and insensitive to AZD8055 group (IC 50 > 0.5 μM) [13]. We also found that insensitive group showed lower mTOR (p < 0.001) expression and lower activity of mTOR complex 1 (p = 0.013) and mTOR complex 2 (p = 0.023) [13]. Cell cycle distribution analysis of NB cell lines was performed by flow cytometry.…”

Section: Inhibition Of Nb Cell Proliferation By Mtor Inhibitormentioning

confidence: 99%

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Molecular Target Therapy against Neuroblastoma

Toyoda¹,

Xu²,

Lei³

et al. 2020

Biophysical Chemistry - Advance Applications

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Neuroblastoma, originated from neural crest cells, is the most common extracranial solid tumor in childhood. Treatment is of limited utility for high-risk neuroblastoma and prognosis is poor. The high incidence of resistance of advancedstage neuroblastoma to conventional therapies has prompt investigators to search for novel therapeutic approaches. Activation of IGF-R/PI3K/Akt/mTOR signaling pathway correlates with oncogenesis, poor prognosis, and chemotherapy resistance in neuroblastoma. Therefore, we investigated the effect of IGF-R/PI3K/Akt/mTOR signaling inhibitors in neuroblastoma. Significantly, IGF-R/PI3K/Akt/mTOR signaling inhibitors effectively inhibited cell growth and induced cell cycle arrest, autophagy, and apoptosis in neuroblastoma cells. Moreover, IGF-R/PI3K/Akt/ mTOR signaling inhibitors significantly reduced tumor growth in mice xenograft model without apparent toxicity. Therefore, these results highlight the potential of IGF-R/PI3K/Akt/mTOR signaling pathway as a promising target for neuroblastoma treatment. Therefore, IGF-1R/PI3K/Akt/mTOR signaling inhibitors should be further investigated for treatment in clinical trials for high-risk neuroblastoma.

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Section: Introductionmentioning

confidence: 55%

Section: Inhibition Of Nb Cell Proliferation By Mtor Inhibitormentioning

confidence: 99%

Section: Inhibition Of Nb Cell Proliferation By Mtor Inhibitormentioning

confidence: 99%

Section: Inhibition Of Nb Cell Proliferation By Mtor Inhibitormentioning

confidence: 99%

Section: Inhibition Of Nb Cell Proliferation By Mtor Inhibitormentioning

confidence: 99%

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Molecular Target Therapy against Neuroblastoma

Toyoda¹,

Xu²,

Lei³

et al. 2020

Biophysical Chemistry - Advance Applications

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Molecular targeting therapies for neuroblastoma: Progress and challenges

Zafar

Wang

Liu

et al. 2020

Medicinal Research Reviews

195

139

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There is an urgent need to identify novel therapies for childhood cancers. Neuroblastoma is the most common pediatric solid tumor, and accounts for ~15% of childhood cancer‐related mortality. Neuroblastomas exhibit genetic, morphological and clinical heterogeneity, which limits the efficacy of existing treatment modalities. Gaining detailed knowledge of the molecular signatures and genetic variations involved in the pathogenesis of neuroblastoma is necessary to develop safer and more effective treatments for this devastating disease. Recent studies with advanced high‐throughput “omics” techniques have revealed numerous genetic/genomic alterations and dysfunctional pathways that drive the onset, growth, progression, and resistance of neuroblastoma to therapy. A variety of molecular signatures are being evaluated to better understand the disease, with many of them being used as targets to develop new treatments for neuroblastoma patients. In this review, we have summarized the contemporary understanding of the molecular pathways and genetic aberrations, such as those in MYCN, BIRC5, PHOX2B, and LIN28B, involved in the pathogenesis of neuroblastoma, and provide a comprehensive overview of the molecular targeted therapies under preclinical and clinical investigations, particularly those targeting ALK signaling, MDM2, PI3K/Akt/mTOR and RAS‐MAPK pathways, as well as epigenetic regulators. We also give insights on the use of combination therapies involving novel agents that target various pathways. Further, we discuss the future directions that would help identify novel targets and therapeutics and improve the currently available therapies, enhancing the treatment outcomes and survival of patients with neuroblastoma.

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Oxadiazol-based mTOR inhibitors with potent antiproliferative activities: synthetic and computational modeling

Khanfar

2022

Mol Divers

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Anti-tumor effect of AZD8055 against neuroblastoma cells in vitro and in vivo

Cited by 24 publications

References 36 publications

Molecular Target Therapy against Neuroblastoma

Molecular Target Therapy against Neuroblastoma

Molecular targeting therapies for neuroblastoma: Progress and challenges

Oxadiazol-based mTOR inhibitors with potent antiproliferative activities: synthetic and computational modeling

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