ArticleCancers2021
Synergistic Drug Combinations Prevent Resistance in ALK+ Anaplastic Large Cell Lymphoma.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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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.
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Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- CircRNAs derived from the tyrosine phosphatase PTPN22 impact chemosensitivity in ALK-positive T-cell lymphomas.Scientific reports · 2026Article
- The molecular mechanisms and potential therapeutic implications of the crosstalk between DNA methylation and metabolic reprogramming in thyroid cancer.Cell death discovery · 2026Review
- BH3 mimetic drugs overcome the microenvironment-induced resistance to crizotinib in ALK+ anaplastic large cell lymphoma.Blood advances · 2025Article
- Recurrent somatic mutations of FAT family cadherins induce an aggressive phenotype and poor prognosis in anaplastic large cell lymphoma.British journal of cancer · 2024Article
- Ageing microenvironment mediates lymphocyte carcinogenesis and lymphoma drug resistance: From mechanisms to clinical therapy (Review).International journal of oncology · 2024Review
- Targeting NRAS via miR-1304-5p or farnesyltransferase inhibition confers sensitivity to ALK inhibitors in ALK-mutant neuroblastoma.Nature communications · 2024Article
- Article
- Gelatin-based cell culture device for construction and X-ray irradiation of a three-dimensional oral cancer model.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2023Article
- Refractory Anaplastic Large Cell Lymphoma Rescued by the Combination of the Second-Generation ALK Inhibitor Brigatinib, High-dose Chemotherapy and Allogeneic Stem Cell Transplantation: A Case Report and Review of the Literature.Clinical hematology international · 2023Review
- Article
- Combination therapy with crizotinib and vinblastine for relapsed or refractory pediatric ALK-positive anaplastic large cell lymphoma.Haematologica · 2023Article
- Tyrosine kinases in nodal peripheral T-cell lymphomas.Frontiers in oncology · 2023Review
- Targeted Epigenetic Interventions in Cancer with an Emphasis on Pediatric Malignancies.Biomolecules · 2022Review
- Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective.Signal transduction and targeted therapy · 2022Review
- Holistic View of ALK TKI Resistance in ALK-Positive Anaplastic Large Cell Lymphoma.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
Anaplastic lymphoma kinase-positive (ALK+) anaplastic large-cell lymphoma (ALCL) is a subtype of non-Hodgkin lymphoma characterized by expression of the oncogenic NPM/ALK fusion protein. When resistant or relapsed to front-line chemotherapy, ALK+ ALCL prognosis is very poor. In these patients, the ALK inhibitor crizotinib achieves high response rates, however 30-40% of them develop further resistance to crizotinib monotherapy, indicating that new therapeutic approaches are needed in this population. We here investigated the efficacy of upfront rational drug combinations to prevent the rise of resistant ALCL, in vitro and in vivo. Different combinations of crizotinib with CHOP chemotherapy, decitabine and trametinib, or with second-generation ALK inhibitors, were investigated. We found that in most cases combined treatments completely suppressed the emergence of resistant cells and were more effective than single drugs in the long-term control of lymphoma cells expansion, by inducing deeper inhibition of oncogenic signaling and higher rates of apoptosis. Combinations showed strong synergism in different ALK-dependent cell lines and better tumor growth inhibition in mice. We propose that drug combinations that include an ALK inhibitor should be considered for first-line treatments in ALK+ ALCL.
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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.