Trial reportBlood2014
IPI-145 antagonizes intrinsic and extrinsic survival signals in chronic lymphocytic leukemia cells.
Trial report in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- Safety and efficacy of dual PI3K-δ, γ inhibitor, duvelisib in patients with relapsed or refractory lymphoid neoplasms: A systematic review and meta-analysis of prospective clinical trials.Frontiers in immunology · 2022Pooled it
- Duvelisib plus romidepsin in relapsed/refractory T cell lymphomas: a phase 1b/2a trial.Nature medicine · 2024Trial
- Trial
- Duvelisib Eliminates CLL B Cells, Impairs CLL-Supporting Cells, and Overcomes Ibrutinib Resistance in a Xenograft Model.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Roles of PI3Kγ and PI3Kδ in mantle cell lymphoma proliferation and migration contributing to efficacy of the PI3Kγ/δ inhibitor duvelisib.Scientific reports · 2023Article
- Circulating Th17 T cells at treatment onset predict autoimmune toxicity of PI3Kδ inhibitors.Blood cancer journal · 2023Article
- Dual inhibition of phosphoinositide 3-kinases delta and gamma reduces chronic B cell activation and autoantibody production in a mouse model of lupus.Frontiers in immunology · 2023Article
- PI3k Inhibitors in NHL and CLL: An Unfulfilled Promise.Blood and lymphatic cancer : targets and therapy · 2023Review
- PI3K Inhibitors for the Treatment of Chronic Lymphocytic Leukemia: Current Status and Future Perspectives.Cancers · 2022Review
- PI3K Isoforms in CD8Current topics in microbiology and immunology · 2022Article
- Review
- Mechanisms of Resistance to PI3K Inhibitors in Cancer: Adaptive Responses, Drug Tolerance and Cellular Plasticity.Cancers · 2021Review
- Oral PI3K-δ,γ Inhibitor for the Management of People with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma: A Narrative Review on Duvelisib.OncoTargets and therapy · 2021Review
- Pathogenesis of chronic lymphocytic leukemia and the development of novel therapeutic strategies.Journal of clinical and experimental hematopathology : JCEH · 2020Review
- The dual PI3Kδ/CK1ε inhibitor umbralisib exhibits unique immunomodulatory effects on CLL T cells.Blood advances · 2020Article
- Phosphoinositide 3-Kinase Signaling in the Tumor Microenvironment: What Do We Need to Consider When Treating Chronic Lymphocytic Leukemia With PI3K Inhibitors?Frontiers in immunology · 2020Review
- Review
- Article
- Targeting PI3K in cancer: mechanisms and advances in clinical trials.Molecular cancer · 2019Review
- The importance of B cell receptor isotypes and stereotypes in chronic lymphocytic leukemia.Leukemia · 2019Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Chronic lymphocytic leukemia (CLL) displays constitutive phosphatidylinositol 3-kinase (PI3K) activation resulting from aberrant regulation of B-cell receptor (BCR) signaling. Previous studies have shown that an oral PI3K p110δ inhibitor idelalisib exhibits promising activity in CLL. Here, we demonstrate that a dual PI3K p110δ and p110γ inhibitor, IPI-145, antagonizes BCR crosslinking activated prosurvival signals in primary CLL cells. IPI-145 causes direct killing in primary CLL cells in a dose- and time-dependent fashion, but does not generate direct cytotoxicity to normal B cells. However, IPI-145 does reduce the viability of normal T and natural killer cells and decrease activated T-cell production of various inflammatory and antiapoptotic cytokines. Furthermore, IPI-145 overcomes the ibrutinib resistance resulting from treatment-induced BTK C481S mutation. Collectively, these studies provide rationale for ongoing clinical evaluation of IPI-145 as a targeted therapy for CLL and related B-cell lymphoproliferative disorders.
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.