Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2025
Protein Profiles Predict Treatment Responses to the PI3K Inhibitor Umbralisib in Patients with Chronic Lymphocytic Leukemia.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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.
A Phase 2 Study to Assess the Safety and Efficacy of TGR-1202 (Umbralisib) in Patients With Chronic Lymphocytic Leukemia (CLL) Who Are Intolerant to Prior BTK or PI3K-Delta Inhibitor Therapy
A Phase 2 Study of Acalabrutinib, Umbralisib, and Ublituximab (AU2) in Relapsed and Previously Untreated CLL Patients
Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Clinical efficacy and safety of umbralisib, a dual PI3Kδ/CK1-ϵ inhibitor, in treatment of hematologic malignancies.Frontiers in oncology · 2025Pooled it
- Article
- Evolution of the drug sensitivity landscape of chronic lymphocytic leukaemia.British journal of haematology · 2026Article
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- Umbralisib antagonizes multidrug resistance in ABCB1-overexpressing cancer cells.Frontiers in oncology · 2026Article
- Integrating molecular targeting and immune modulation in triple-negative breast cancer: from mechanistic insights to therapeutic innovation.Frontiers in immunology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
purposeThe management of chronic lymphocytic leukemia (CLL) has significantly improved with targeted therapies. However, many patients experience a suboptimal response. To optimally select the best therapy, predictive biomarkers are necessary. In this study, we used the phosphoinositide 3-kinase (PI3K) inhibitor umbralisib as a model to (i) understand the impact of targeted treatment on cell signaling and immunophenotypes in responders and nonresponders, (ii) identify molecular features that predict individual treatment responses, and (iii) suggest alternative treatment options for the nonresponders. EXPERIMENTAL
designWe performed functional phenotyping of CLL cells from patients enrolled in two clinical trials with umbralisib, administered either as a monotherapy (NCT02742090, n = 55) or in combination with the Bruton tyrosine kinase (BTK) inhibitor acalabrutinib (NCT04624633, n = 12).
resultsWe found that umbralisib monotherapy led to significant changes in (phospho)protein levels, including AKT (pS473), in responders but not in nonresponders. Furthermore, the proportion of cytotoxic natural killer (NK) cells increased at the end of the study but only in responders, suggesting a role in the antitumor response. To identify molecular predictors of response, we used the baseline levels of 30 (phospho)proteins in the monotherapy cohort as input features for a machine learning model, which achieved significant prediction accuracy in cross-validation and maintained its predictive power in the combination cohort. Drug sensitivity profiling of the CLL cells at baseline suggested that PI3K + Bcl-2 inhibitors are effective in umbralisib nonresponders.
conclusionsFunctional phenotyping reveals differential cellular responses to umbralisib treatment in responders and nonresponders; predicts treatment response of individual patients with CLL; and suggests alternative treatment options for the nonresponders.
Indexed as
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What Socratic 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 Socratic graph.