Vitamin K3 derivative induces apoptotic cell death in neuroblastoma via downregulation of MYCN expression

Yoda, Hiroyuki; Nakayama, Toshimitsu; Miura, Motofumi; Toriyama, Masaharu; Motohashi, Shigeyasu; Suzuki, Takashi

doi:10.1016/j.bbrep.2019.100701

Cited by 2 publications

(2 citation statements)

References 31 publications

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“…Bortezomib has also been found to inhibit LIN28B expression, and the combination of bortezomib and DFMO leads to more significant inhibition of LIN28B expression in NB cells than treatment with either agent alone 209 . A derivative of vitamin K3 (VK3‐OH) has also been found to suppress LIN28B at the protein as well as mRNA levels in MYCN‐driven NB cells 210 . Further, JQ1 and panobinostat have been found to synergistically downregulate the gene expression of LIN28B and protein expression of N‐Myc in NB cells 211 .…”

Section: Preclinical Studies Of Targeted Nb Therapymentioning

confidence: 99%

Molecular targeting therapies for neuroblastoma: Progress and challenges

Zafar

Wang

Liu

et al. 2020

Medicinal Research Reviews

191

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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Section: Preclinical Studies Of Targeted Nb Therapymentioning

confidence: 99%

Molecular targeting therapies for neuroblastoma: Progress and challenges

Zafar

Wang

Liu

et al. 2020

Medicinal Research Reviews

191

139

View full text Add to dashboard Cite

show abstract

“…These are partially discussed below; a partial list is presented in Table 1. Third-generation ALK inhibitor repotrectinib (TPX-0005, currently in Phase I, Phase II trials) targets the active kinase conformations of ALK, ROS1, and NTRK1-3; impedes proliferation and prompts apoptosis in ALK-addicted NB cells; and inhibits ALK-driven neurite outgrowth and prompts tumor regression [117]. Vitamin K3 derivative (VK3-OH) induces apoptosis through activation of TS-p53, and downregulates Bcl-2 and Mcl-1 in MYCN-driven NB cells [118].…”

Section: Drugs and Strategies In Developmentmentioning

confidence: 99%

Emerging therapeutic targets for neuroblastoma

Aravindan

Herman

Aravindan

2020

Expert Opinion on Therapeutic Targets

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Introduction: Neuroblastoma (NB) is the prime cancer of infancy, and accounts for 9% of pediatric cancer deaths. While children diagnosed with clinically stable NB experience a complete cure, those with high-risk disease (HR-NB) do not recover, despite intensive therapeutic strategies. Development of novel and effective targeted therapies is needed to counter disease progression, and to benefit long-term survival of children with HR-NB. Areas covered:Recent studies (2017-2020) pertinent to NB evolution are selectively reviewed to recognize novel and effective therapeutic targets. The prospective and promising therapeutic targets/strategies for HR-NB are categorized into (a) targeting oncogene-like and/or reinforcing tumor suppressor (TS)-like lncRNAs; (b) targeting oncogene-like microRNAs (miRs) and/or mimicking TS-miRs; (c) targets for immunotherapy; (d) targeting epithelial-to-mesenchymal transition and cancer stem cells; (e) novel and beneficial combination approaches; and (f) repurposing drugs and other strategies in development.Expert opinion: It is highly unlikely that agents targeting a single candidate or signaling will be beneficial for an HR-NB cure. We must develop efficient drug deliverables for functional targets, which could be integrated and advance clinical therapy. Fittingly, the looming evidence indicated an aggressive evolution of promising novel and integrative targets, development of efficient drugs, and improvised strategies for HR-NB treatment.

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Vitamin K3 derivative induces apoptotic cell death in neuroblastoma via downregulation of MYCN expression

Cited by 2 publications

References 31 publications

Molecular targeting therapies for neuroblastoma: Progress and challenges

Molecular targeting therapies for neuroblastoma: Progress and challenges

Emerging therapeutic targets for neuroblastoma

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