ArticlePloS one2017
PI3Kδ inhibitor idelalisib in combination with BTK inhibitor ONO/GS-4059 in diffuse large B cell lymphoma with acquired resistance to PI3Kδ and BTK inhibitors.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02457598 (A Phase 1b Dose Escalation and Dose Expansion Study of Tirabrutinib), which is not on this map. Cited by 30 papers.
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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.
A Phase 1b Dose Escalation and Dose Expansion Study of Tirabrutinib (ONO/GS-4059) in Combination With Other Targeted Anti-cancer Therapies in Subjects With B-cell Malignancies
Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
- Bruton Tyrosine Kinase Inhibition: an Effective Strategy to Manage Waldenström Macroglobulinemia.Current hematologic malignancy reports · 2024Review
- Safety and efficacy of zandelisib plus zanubrutinib in previously treated follicular and mantle cell lymphomas.British journal of haematology · 2024Article
- Functional impact and molecular binding modes of drugs that target the PI3K isoform p110δ.Communications biology · 2023Article
- Metabolic Reprogramming and Potential Therapeutic Targets in Lymphoma.International journal of molecular sciences · 2023Review
- Bruton's Tyrosine Kinase Inhibitors (BTKIs): Review of Preclinical Studies and Evaluation of Clinical Trials.Molecules (Basel, Switzerland) · 2023Review
- Article
- Resistance to PI3Kδ inhibitors in marginal zone lymphoma can be reverted by targeting the IL-6/PDGFRA axis.Haematologica · 2022Article
- Altered pathways and targeted therapy in double hit lymphoma.Journal of hematology & oncology · 2022Review
- PI3K inhibitors are finally coming of age.Nature reviews. Drug discovery · 2021Review
- Immune targeted therapy for diffuse large B cell lymphoma.Blood science (Baltimore, Md.) · 2021Review
- An Overview on Diffuse Large B-Cell Lymphoma Models: Towards a Functional Genomics Approach.Cancers · 2021Review
- Diagnostic significance of circulating miR-485-5p in patients with lupus nephritis and its predictive value evaluation for the clinical outcomes.Journal of the Chinese Medical Association : JCMA · 2021Article
- Ibrutinib combinations in CLL therapy: scientific rationale and clinical results.Blood cancer journal · 2021Review
- Article
- Tirabrutinib: First Approval.Drugs · 2020Review
- Development of Pyrazolo[3,4-ACS medicinal chemistry letters · 2020Article
- Cell line-based assessment of BTK inhibitors.British journal of pharmacology · 2020Article
- Preclinical Evaluation of a Novel SHIP1 Phosphatase Activator for Inhibition of PI3K Signaling in Malignant B Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Copanlisib synergizes with conventional and targeted agents including venetoclax in B- and T-cell lymphoma models.Blood advances · 2020Article
- Discovery and biological evaluation of N-(3-(7-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)-4-methyl-2-oxo-2H-pyrimido[4,5-d][1,3]oxazin-1(4H)-yl)phenyl)acrylamide as potent Bruton's tyrosine kinase inhibitors.Acta pharmacologica Sinica · 2020Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activated B-cell-like diffuse large B-cell lymphoma relies on B-cell receptor signaling to drive proliferation and survival. Downstream of the B-cell receptor, the key signaling kinases Bruton's tyrosine kinase and phosphoinositide 3-kinase δ offer opportunities for therapeutic intervention by agents such as ibrutinib, ONO/GS-4059, and idelalisib. Combination therapy with such targeted agents could provide enhanced efficacy due to complimentary mechanisms of action. In this study, we describe both the additive interaction of and resistance mechanisms to idelalisib and ONO/GS-4059 in a model of activated B-cell-like diffuse large B-cell lymphoma. Significant tumor regression was observed with a combination of PI3Kδ and Bruton's tyrosine kinase inhibitors in the mouse TMD8 xenograft. Acquired resistance to idelalisib in the TMD8 cell line occurred by loss of phosphatase and tensin homolog and phosphoinositide 3-kinase pathway upregulation, but not by mutation of PIK3CD. Sensitivity to idelalisib could be restored by combining idelalisib and ONO/GS-4059. Further evaluation of targeted inhibitors revealed that the combination of idelalisib and the phosphoinositide-dependent kinase-1 inhibitor GSK2334470 or the AKT inhibitor MK-2206 could partially overcome resistance. Characterization of acquired Bruton's tyrosine kinase inhibitor resistance revealed a novel tumor necrosis factor alpha induced protein 3 mutation (TNFAIP3 Q143*), which led to a loss of A20 protein, and increased p-IκBα. The combination of idelalisib and ONO/GS-4059 partially restored sensitivity in this resistant line. Additionally, a mutation in Bruton's tyrosine kinase at C481F was identified as a mechanism of resistance. The combination activity observed with idelalisib and ONO/GS-4059, taken together with the ability to overcome resistance, could lead to a new therapeutic option in activated B-cell-like diffuse large B-cell lymphoma. A clinical trial is currently underway to evaluate the combination of idelalisib and ONO/GS-4059 (NCT02457598).
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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.