ArticleInternational journal of cancer2017
Mutation in the FGFR1 tyrosine kinase domain or inactivation of PTEN is associated with acquired resistance to FGFR inhibitors in FGFR1-driven leukemia/lymphomas.
Article in International journal of cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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
35 citing papers in PubMed, 70 citations in OpenAlex.
- Discovery and Characterization of Novel FGFR1 V561M Inhibitors via Virtual Screening and Molecular Dynamics Simulations.ACS medicinal chemistry letters · 2025Article
- Pharmacological and Biological Targeting of FGFR1 in Cancer.Current issues in molecular biology · 2024Review
- Mechanisms of resistance to tyrosine kinase inhibitor-targeted therapy and overcoming strategies.MedComm · 2024Review
- Single-cell analysis defines highly specific leukemia-induced neutrophils and links MMP8 expression to recruitment of tumor associated neutrophils during FGFR1 driven leukemogenesis.Experimental hematology & oncology · 2024Article
- FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions.Nature reviews. Clinical oncology · 2024Review
- Biology and Therapeutic Properties of Mesenchymal Stem Cells in Leukemia.International journal of molecular sciences · 2024Review
- Molecular Targeting of the Fibroblast Growth Factor Receptor Pathway across Various Cancers.International journal of molecular sciences · 2024Review
- ATF4 renders human T-cell acute lymphoblastic leukemia cell resistance to FGFR1 inhibitors through amino acid metabolic reprogramming.Acta pharmacologica Sinica · 2023Article
- RHOA-regulated IGFBP2 promotes invasion and drives progression of BCR-ABL1 chronic myeloid leukemia.Haematologica · 2023Article
- Treatment approaches for FGFR-altered urothelial carcinoma: targeted therapies and immunotherapy.Frontiers in immunology · 2023Review
- Review
- Blockade of FGF2/FGFR2 partially overcomes bone marrow mesenchymal stromal cells mediated progression of T-cell acute lymphoblastic leukaemia.Cell death & disease · 2022Article
- Review
- A truncated derivative of FGFR1 kinase cooperates with FLT3 and KIT to transform hematopoietic stem cells in syndromic and de novo AML.Molecular cancer · 2022Article
- Review
- New Directions and Challenges in Targeted Therapies of Advanced Bladder Cancer: The Role of FGFR Inhibitors.Cancers · 2022Review
- Review
- Fibroblast growth factor receptors in cancer: genetic alterations, diagnostics, therapeutic targets and mechanisms of resistance.British journal of cancer · 2021Review
- FGFR-TKI resistance in cancer: current status and perspectives.Journal of hematology & oncology · 2021Review
- Dual activating FGFR1 mutations in pediatric pilomyxoid astrocytoma.Molecular genetics & genomic medicine · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Stem cell leukemia/lymphoma syndrome (SCLL) is driven by constitutive activation of chimeric FGFR1 kinases generated by chromosome translocations. We have shown that FGFR inhibitors significantly suppress leukemia and lymphoma development in vivo, and cell viability in vitro. Since resistance to targeted therapies is a major reason for relapse, we developed FGFR1-overexpressing mouse and human cell lines that are resistant to the specific FGFR inhibitors AZD4547 and BGJ398, as well as non-specific inhibitors, such as ponatinib, TKI258 and E3810. Two mutually exclusive mechanisms for resistance were demonstrated; an activating V561M mutation in the FGFR1 kinase domain and mutational inactivation of PTEN resulting in increased PI3K/AKT activity. Ectopic expression of PTEN in the PTEN-mutant cells resensitizes them to FGFR inhibitors. Treatment of resistant cells with BGJ398, in combination with the BEZ235 PI3K inhibitor, shows an additive effect on growth in vitro and prolongs survival in xenograft models in vivo. These studies provide the first direct evidence for both the involvement of the FGFR1 V561M mutation and PTEN inactivation in the development of resistance in leukemias overexpressing chimeric FGFR1. These studies also provide a potential strategy to treat leukemias and lymphomas driven by FGFR1 activation that become resistant to FGFR1 inhibitors.
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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.