ArticleJournal of cancer research and clinical oncology2014
Activating mutations in ALK kinase domain confer resistance to structurally unrelated ALK inhibitors in NPM-ALK-positive anaplastic large-cell lymphoma.
Article in Journal of cancer research and clinical oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Anaplastic large cell lymphoma in children and adolescents.British journal of haematology · 2025Review
- Acquired L1196MEJHaem · 2023Article
- Lymphomatous Meningitis From Anaplastic Lymphoma Kinase+ Anaplastic Large T-Cell Lymphoma Treated With Lorlatinib: A Case Report.JCO precision oncology · 2022Article
- Review
- Review
- Activation of IGF-1R pathway and NPM-ALK G1269A mutation confer resistance to crizotinib treatment in NPM-ALK positive lymphoma.Investigational new drugs · 2020Article
- CDC37 as a novel target for the treatment of NPM1-ALK expressing anaplastic large cell lymphomas.Blood cancer journal · 2019Article
- Review
- From Pathology to Precision Medicine in Anaplastic Large Cell Lymphoma Expressing Anaplastic Lymphoma Kinase (ALK+ ALCL).Cancers · 2017Review
- TrkA is a binding partner of NPM-ALK that promotes the survival of ALKMolecular oncology · 2017Article
- Targeting ALK: Precision Medicine Takes on Drug Resistance.Cancer discovery · 2017Review
- The use of cellular thermal shift assay (CETSA) to study Crizotinib resistance in ALK-expressing human cancers.Scientific reports · 2016Article
- MultiDimensional ClinOmics for Precision Therapy of Children and Adolescent Young Adults with Relapsed and Refractory Cancer: A Report from the Center for Cancer Research.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Excess of NPM-ALK oncogenic signaling promotes cellular apoptosis and drug dependency.Oncogene · 2016Article
- Three Years Sustained Complete Remission Achieved in a Primary Refractory ALK-Positive Anaplastic T Large Cell Lymphoma Treated with Crizotinib.Rare tumors · 2016Article
- TKI sensitivity patterns of novel kinase-domain mutations suggest therapeutic opportunities for patients with resistant ALK+ tumors.Oncotarget · 2016Article
- Nanotechnology applications in hematological malignancies (Review).Oncology reports · 2015Review
- Reversal of microRNA-150 silencing disadvantages crizotinib-resistant NPM-ALK(+) cell growth.The Journal of clinical investigation · 2015Article
- Evidence Suggesting That Discontinuous Dosing of ALK Kinase Inhibitors May Prolong Control of ALK+ Tumors.Cancer research · 2015Article
- NPM/ALK mutants resistant to ASP3026 display variable sensitivity to alternative ALK inhibitors but succumb to the novel compound PF-06463922.Oncotarget · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeCrizotinib, the first FDA-approved ALK inhibitor, showed significant antitumor activity in young patients with anaplastic large-cell lymphoma (ALCL) frequently displaying ALK rearrangement. However, long-term therapeutic benefits of crizotinib are limited due to development of drug resistance. CH5424802--more potent and selective ALK inhibitor--comprises a good candidate for second-line treatment in crizotinib-relapsed patients. The aim of this study was to determine possible mechanisms of resistance to ALK inhibitors that can appear in ALCL patients.
methodsALK+ ALCL cell lines resistant to crizotinib (Karpas299CR) and to CH5424802 (Karpas299CHR) were established by long-term exposure of Karpas299 cells to these inhibitors. Next, alterations in their sensitivity to ALK, HSP90 and mTOR inhibitors were investigated by cell viability and BrdU incorporation assays and immunoblot analysis.
resultscDNA sequencing of ALK kinase domain revealed activating mutations-I1171T in Karpas299CR and F1174C in Karpas299CHR. The resistant cells displayed diminished sensitivity to structurally unrelated ALK inhibitors-crizotinib, CH5424802 and TAE684. Nevertheless, CH5424802 and TAE684 were still more potent against the resistant cells than crizotinib. Moreover, Karpas299CR and Karpas299CHR cells remained sensitive to HSP90 or mTOR inhibitors.
conclusionsResistance mediated by activating mutations in ALK kinase domain may emerge in ALCL patients during ALK inhibitors treatment. However, more potent second-generation ALK inhibitors, HSP90 or mTOR inhibitors may represent an effective therapy for relapsed ALK+ ALCL patients.
Indexed as
Identifiers
What OpenQuestion holds
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.