ArticleOncotarget2016
Smac mimetic LCL161 supports neuroblastoma chemotherapy in a drug class-dependent manner and synergistically interacts with ALK inhibitor TAE684 in cells with ALK mutation F1174L.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- IAP antagonists induce anti-tumor immunity in multiple myeloma.Nature medicine · 2016Trial
- Targeting "undruggable" cancer proteins: pharmacological challenges and emerging strategies.Translational cancer research · 2026Review
- Purification of Lepidilines A, B, C, and D fromMolecules (Basel, Switzerland) · 2025Article
- Research Progress in the Small Molecule Smac Mimetics in Combination Therapy of Cancer.Current medicinal chemistry · 2025Review
- A Phase Ib Dose-Escalation Study of LCL161 Plus Oral Topotecan for Patients With Relapsed/Refractory Small Cell Lung Cancer and Select Gynecologic Malignancies.The oncologist · 2023Article
- Targeting the apoptosis pathway to treat tumours of the paediatric nervous system.Cell death & disease · 2022Review
- Synthetic Heterocyclic Derivatives as Kinase Inhibitors Tested for the Treatment of Neuroblastoma.Molecules (Basel, Switzerland) · 2021Review
- Molecular and Functional Characterization of Inhibitor of Apoptosis Proteins (IAP, BIRP) inFrontiers in microbiology · 2020Article
- In Search of Panacea-Review of Recent Studies Concerning Nature-Derived Anticancer Agents.Nutrients · 2019Review
- The SMAC mimetic LCL-161 displays antitumor activity in preclinical models of rituximab-resistant B-cell lymphoma.Blood advances · 2018Article
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroblastoma is the most common extracranial solid tumor during infancy and childhood.Outcome of high-risk and late-stage disease remains poor despite intensive treatment regimens.Suppressing inhibitor of apoptosis proteins (IAPs) using Smac mimetics (SM) significantly sensitizes neuroblastoma (NB) cells for chemotherapy, however strongly dependent on the cytotoxic drug combined with SM.Therefore, a systematic analysis of the impact of SM in combination with different classes of chemotherapeutics was of crucial importance. Treatment of NB cell lines with SM LCL161 and vinca alkaloids revealed a strong synergistic inhibition of proliferation and significant induction of apoptosis in virtually all established and de novo NB cell lines (n=8).In contrast, combination of anthracyclines or topoisomerase inhibitors with LCL161 showed a synergism for single drugs and/or cell lines only.Furthermore, we could show that insensibility to LCL161-mediated sensitization for chemotherapeutics is associated with aberrant activation of anaplastic lymphoma kinase (ALK) by common mutation F1174L. Inhibition of ALK using TAE684 is able to overcome this resistance in a synergistic fashion, a finding that could be highly relevant for improvement of neuroblastoma therapy.
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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.