ArticleMolecular cancer therapeutics2013
Novel treatment for mantle cell lymphoma including therapy-resistant tumor by NF-κB and mTOR dual-targeting approach.
Article in Molecular cancer therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
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- Marinopyrrole derivative MP1 as a novel anti-cancer agent in group 3 MYC-amplified Medulloblastoma.Journal of experimental & clinical cancer research : CR · 2024Article
- A novel dual epigenetic approach targeting BET proteins and HDACs in Group 3 (MYC-driven) Medulloblastoma.Journal of experimental & clinical cancer research : CR · 2022Article
- Small-molecule IKKβ activation modulator (IKAM) targets MAP3K1 and inhibits pancreatic tumor growth.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Structure activity relationship (SAR) study identifies a quinoxaline urea analog that modulates IKKβ phosphorylation for pancreatic cancer therapy.European journal of medicinal chemistry · 2021Article
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- Small molecule binding to inhibitor of nuclear factor kappa-B kinase subunit beta in an ATP non-competitive manner.Chemical communications (Cambridge, England) · 2021Article
- Role of protein arginine methyltransferase 5 in group 3 (MYC-driven) Medulloblastoma.BMC cancer · 2019Article
- Observational
- Article
- Improved therapy for medulloblastoma: targeting hedgehog and PI3K-mTOR signaling pathways in combination with chemotherapy.Oncotarget · 2018Article
- ZGDHu-1 promotes apoptosis of mantle cell lymphoma cells.Oncotarget · 2017Article
- Mantle cell lymphoma in the era of precision medicine-diagnosis, biomarkers and therapeutic agents.Oncotarget · 2016Review
- Isatin Derived Spirocyclic Analogues with α-Methylene-γ-butyrolactone as Anticancer Agents: A Structure-Activity Relationship Study.Journal of medicinal chemistry · 2016Article
- Article
- Improved therapy for neuroblastoma using a combination approach: superior efficacy with vismodegib and topotecan.Oncotarget · 2016Article
- [Advances of aberrant signaling pathways and related targeting drugs in B cell non- Hodgkin lymphoma].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2015Article
- A quinoxaline urea analog uncouples inflammatory and pro-survival functions of IKKβ.Immunology letters · 2015Article
- Assessment of caroverine as a potential chemotherapeutical agent in HNSCC cell lines.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2015Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Mantle cell lymphoma (MCL) is one of the most aggressive B-cell non-Hodgkin lymphomas with a median survival of approximately five years. Currently, there is no curative therapy available for refractory MCL because of relapse from therapy-resistant tumor cells. The NF-κB and mTOR pathways are constitutively active in refractory MCL leading to increased proliferation and survival. Targeting these pathways is an ideal strategy to improve therapy for refractory MCL. Therefore, we investigated the in vitro and in vivo antilymphoma activity and associated molecular mechanism of action of a novel compound, 13-197, a quinoxaline analog that specifically perturbs IκB kinase (IKK) β, a key regulator of the NF-κB pathway. 13-197 decreased the proliferation and induced apoptosis in MCL cells including therapy-resistant cells compared with control cells. Furthermore, we observed downregulation of IκBα phosphorylation and inhibition of NF-κB nuclear translocation by 13-197 in MCL cells. In addition, NF-κB-regulated genes such as cyclin D1, Bcl-XL, and Mcl-1 were downregulated in 13-197-treated cells. In addition, 13-197 inhibited the phosphorylation of S6K and 4E-BP1, the downstream molecules of mTOR pathway that are also activated in refractory MCL. Further, 13-197 reduced the tumor burden in vivo in the kidney, liver, and lungs of therapy-resistant MCL-bearing nonobese diabetic severe-combined immunodeficient (NOD/SCID) mice compared with vehicle-treated mice; indeed, 13-197 significantly increased the survival of MCL-transplanted mice. Together, results suggest that 13-197 as a single agent disrupts the NF-κB and mTOR pathways leading to suppression of proliferation and increased apoptosis in malignant MCL cells including reduction in tumor burden in mice.
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