ArticleOncotarget2015
NPM/ALK mutants resistant to ASP3026 display variable sensitivity to alternative ALK inhibitors but succumb to the novel compound PF-06463922.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- OKAIN: A comprehensive oncology knowledge base for the interpretation of clinically actionable alterations.Open medicine (Warsaw, Poland) · 2025Article
- Anaplastic Lymphoma Kinase (ALK) Inhibitors Enhance Phagocytosis Induced by CD47 Blockade in Sensitive and Resistant ALK-Driven Malignancies.Biomedicines · 2024Article
- Article
- Update of Diagnosis and Targeted Therapy for ALKCurrent treatment options in oncology · 2023Review
- Acquired ALK G1202R-, ALK I1171N-, or EML4-ALK-mediated resistance to ensartinib in lung adenocarcinoma but responded to lorlatinib: A case report.Frontiers in oncology · 2023Article
- Case report: Durable response to alectinib inFrontiers in oncology · 2022Article
- 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
- Dual inhibition of IGF-IR and ALK as an effective strategy to eradicate NPM-ALKJournal of hematology & oncology · 2019Article
- Anaplastic lymphoma kinase fusions: Roles in cancer and therapeutic perspectives.Oncology letters · 2019Review
- Chinese perspectives on clinical efficacy and safety of alectinib in patients withOncoTargets and therapy · 2019Article
- Article
- Xenograft tumors derived from malignant pleural effusion of the patients with non-small-cell lung cancer as models to explore drug resistance.Cancer communications (London, England) · 2018Article
- Data driven polypharmacological drug design for lung cancer: analyses for targeting ALK, MET, and EGFR.Journal of cheminformatics · 2017Article
- T-cell lymphomas, a challenging disease: types, treatments, and future.International journal of clinical oncology · 2017Review
- ALK: a tyrosine kinase target for cancer therapy.Cold Spring Harbor molecular case studies · 2017Review
- Synergistic activity of ALK and mTOR inhibitors for the treatment of NPM-ALK positive lymphoma.Oncotarget · 2016Article
- Excess of NPM-ALK oncogenic signaling promotes cellular apoptosis and drug dependency.Oncogene · 2016Article
- TKI sensitivity patterns of novel kinase-domain mutations suggest therapeutic opportunities for patients with resistant ALK+ tumors.Oncotarget · 2016Article
- Management of advanced non-small cell lung cancers with known mutations or rearrangements: latest evidence and treatment approaches.Therapeutic advances in respiratory disease · 2016Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ALK is involved in the onset of several tumors. Crizotinib (XalkoriTM), a potent ALK inhibitor, represents the current front-line treatment for ALK+ NSCLC and shows great clinical efficacy. However, resistant disease often develops after initial response. ASP3026 is a novel second-generation ALK inhibitor with activity on crizotinib-resistant ALK-L1196M gatekeeper mutant. As resistance is likely to be a relevant hurdle for any drug, we sought to determine the resistance profile of ASP3026 in the context of NPM/ALK+ ALCL. We selected six ASP3026-resistant cell lines by culturing human ALCL cells in the presence of increasing concentrations of drug. The established resistant cell lines carry several point mutations in the ALK kinase domain (G1128S, C1156F, I1171N/T, F1174I, N1178H, E1210K and C1156F/D1203N were the most frequent) that are shown to confer resistance to ASP3026 in the Ba/F3 cell model. All mutants were profiled for cross-resistance against a panel of clinically relevant inhibitors including ceritinib, alectinib, crizotinib, AP26113 and PF-06463922. Finally, a genetically heterogeneous ASP3026-resistant cell line was exposed to second-line treatment simulations with all inhibitors. The population evolved according to relative sensitivity of its mutant subclones to the various drugs. Compound PF-06463922 did not allow the outgrowth of any resistant clone, at non-toxic doses.
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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.