ReviewClinical cancer research : an official journal of the American Association for Cancer Research2024
PI3K Inhibitors in Hematology: When One Door Closes….
Review in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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Who cites it
19 citing papers in PubMed.
- Protein Profiles Predict Treatment Responses to the PI3K Inhibitor Umbralisib in Patients with Chronic Lymphocytic Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- The conformation-selective PI3Kδ inhibitor roginolisib in patients with advanced or metastatic cancer, including metastatic uveal melanoma: first-in-human clinical trial.Nature communications · 2026Article
- Article
- PIK3CA mutations and PI3K isoform expression define prognostic signatures in ovarian clear cell carcinoma.Archives of gynecology and obstetrics · 2026Article
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- The PI3Kδ inhibitor roginolisib (IOA-244) preserves T-cell function and activity.Molecular oncology · 2026Article
- CD40/PI3K/FOXO1 axis rewiring drives microenvironment-dependent BIM silencing to sustain lymphoma growth and survival.Leukemia · 2026Article
- Clinical trial success rate in lymphoma: fate of trials and agents from 2000 to 2019.Blood advances · 2026Article
- Phosphatidylinositol-3-Kinase (PI3K) and Histone Deacetylase (HDAC) Multitarget Inhibitors: An Update on Clinical and Preclinical Candidates.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Molecularly targeted therapy and immunotherapy in leukemias.Journal of hematology & oncology · 2026Review
- From PIK3CA Mutations to Rational PI3K Inhibition for the Treatment of Colorectal Cancer.Molecular diagnosis & therapy · 2026Review
- Umbralisib antagonizes multidrug resistance in ABCB1-overexpressing cancer cells.Frontiers in oncology · 2026Article
- RNA processing kinase inhibitors and epigenetic inhibitors in combination with oncology drugs or investigational agents in multi-cell type patient-derived tumor cell line spheroids.Cancer chemotherapy and pharmacology · 2025Article
- Proteasome inhibition overcomes resistance to targeted therapies in B-cell malignancy models and in an index patient.Cell death & disease · 2025Article
- Review
- Chronic Lymphocytic Leukemia: 2025 Update on the Epidemiology, Pathogenesis, Diagnosis, and Therapy.American journal of hematology · 2025Review
- Targeting PI3Kδ in cancer: a setback or the end.Frontiers in oncology · 2025Article
- RAS signaling in carcinogenesis, cancer therapy and resistance mechanisms.Journal of hematology & oncology · 2024Review
- Expert insights on Hodgkin's lymphoma development in an activated PI3K delta syndrome patient undergoing leniolisib treatment.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
The PI3K signaling pathway regulates key cellular processes and is one of the most aberrantly activated pathways in cancer. The class I PI3K catalytic subunits p110γ and p110δ are highly enriched in leukocytes, providing an additional rationale for targeting these PI3Ks in hematologic malignancies. In 2014, the PI3Kδ inhibitor idelalisib was the first of four PI3K inhibitors (PI3Ki) to receive regulatory approval for relapsed B-cell malignancies. This was followed by approvals of the pan-class I inhibitor copanlisib (2017), the dual PI3Kγ/δ inhibitor duvelisib (2018), and the PI3Kδ and casein kinase 1ε inhibitor umbralisib (2021). Copanlisib and umbralisib received accelerated approvals, whereas idelalisib and duvelisib received initial accelerated approvals followed by full approvals. The accelerated approvals were based on overall response rates; however, follow-up studies showed increased risk of death and serious side effects. Furthermore, the confirmatory trial with copanlisib failed to show an improvement in progression-free survival when compared with chemoimmunotherapy. These developments led to black box warnings for idelalisib and duvelisib and withdrawal of copanlisib and umbralisib from the market by their manufacturers. Given the uncertain future of this drug class, additional manufacturers terminated ongoing phase III trials with novel PI3Kis. In this study, we review the development and current status of PI3Kis in hematology, limitations to their use, and our perspective on whether there is a future for PI3Kis in hematology.
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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.