ArticleApoptosis : an international journal on programmed cell death2015
mTOR ATP-competitive inhibitor INK128 inhibits neuroblastoma growth via blocking mTORC signaling.
Article in Apoptosis : an international journal on programmed cell death, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 48 citations in OpenAlex.
- Unveiling Novel Avenues in mTOR-Targeted Therapeutics: Advancements in Glioblastoma Treatment.International journal of molecular sciences · 2023Review
- Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.Pharmaceutics · 2023Review
- mTOR as a Potential Target for the Treatment of Microbial Infections, Inflammatory Bowel Diseases, and Colorectal Cancer.International journal of molecular sciences · 2022Review
- MYCN Impact on High-Risk Neuroblastoma: From Diagnosis and Prognosis to Targeted Treatment.Cancers · 2022Review
- Metabolic Reprogramming in Cancer Cells: Emerging Molecular Mechanisms and Novel Therapeutic Approaches.Pharmaceutics · 2022Review
- Neuroblastoma Cell Death Induced by eEF1A2 Knockdown Is Possibly Mediated by the Inhibition of Akt and mTOR Phosphorylation.International journal of hematology-oncology and stem cell research · 2021Article
- Integrated Genomic Profiling and Drug Screening of Patient-Derived Cultures Identifies Individualized Copy Number-Dependent Susceptibilities Involving PI3K Pathway and 17q Genes in Neuroblastoma.Frontiers in oncology · 2021Article
- The Anti-Non-Small Cell Lung Cancer Cell Activity by a mTOR Kinase Inhibitor PQR620.Frontiers in oncology · 2021Article
- Article
- Targeting the Mitochondrial Metabolic Network: A Promising Strategy in Cancer Treatment.International journal of molecular sciences · 2020Review
- Lowe syndrome patient cells display mTOR- and RhoGTPase-dependent phenotypes alleviated by rapamycin and statins.Human molecular genetics · 2020Article
- The role of RICTOR amplification in targeted therapy and drug resistance.Molecular medicine (Cambridge, Mass.) · 2020Review
- MiR-199a-modified exosomes from adipose tissue-derived mesenchymal stem cells improve hepatocellular carcinoma chemosensitivity through mTOR pathway.Journal of experimental & clinical cancer research : CR · 2020Article
- Inactivation of mTORC2 in macrophages is a signature of colorectal cancer that promotes tumorigenesis.JCI insight · 2019Article
- Mechanisms of autophagy and relevant small-molecule compounds for targeted cancer therapy.Cellular and molecular life sciences : CMLS · 2018Review
- Cell death-based treatment of neuroblastoma.Cell death & disease · 2018Review
- Small molecule inhibitor regorafenib inhibits RET signaling in neuroblastoma cells and effectively suppresses tumor growthOncotarget · 2017Article
- EWS-FLI1 and RNA helicase A interaction inhibitor YK-4-279 inhibits growth of neuroblastoma.Oncotarget · 2017Article
- The dual mTOR kinase inhibitor TAK228 inhibits tumorigenicity and enhances radiosensitization in diffuse intrinsic pontine glioma.Cancer letters · 2017Article
- Novel multiple tyrosine kinase inhibitor ponatinib inhibits bFGF-activated signaling in neuroblastoma cells and suppresses neuroblastoma growth in vivo.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
High-risk neuroblastoma often develops resistance to high-dose chemotherapy. The mTOR signaling cascade is frequently deregulated in human cancers and targeting mTOR signaling sensitizes many cancer types to chemotherapy. Here, using a panel of neuroblastoma cell lines, we found that the mTOR inhibitor INK128 showed inhibitory effects on both anchorage-dependent and independent growth of neuroblastoma cells and significantly enhanced the cytotoxic effects of doxorubicin (Dox) on these cell lines. Treatment of neuroblastoma cells with INK128 blocked the activation of downstream mTOR signaling and enhanced Dox-induced apoptosis. Moreover, INK128 was able to overcome the established chemoresistance in the LA-N-6 cell line. Using an orthotopic neuroblastoma mouse model, we found that INK128 significantly inhibited tumor growth in vivo. In conclusion, we have shown that INK128-mediated mTOR inhibition possessed substantial antitumor activity and could significantly increase the sensitivity of neuroblastoma cells to Dox therapy. Taken together, our results indicate that using INK128 can provide additional efficacy to current chemotherapeutic regimens and represent a new paradigm in restoring drug sensitivity in neuroblastoma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.