ArticleLeukemia2020
An in vitro assay for biomarker discovery and dose prediction applied to ibrutinib plus venetoclax treatment of CLL.
Article in Leukemia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- Evolution of the drug sensitivity landscape of chronic lymphocytic leukaemia.British journal of haematology · 2026Article
- Proteasome inhibition overcomes resistance to targeted therapies in B-cell malignancy models and in an index patient.Cell death & disease · 2025Article
- Gene Expression Analysis and Validation of a Novel Biomarker Signature for Early-Stage Lung Adenocarcinoma.Biomolecules · 2025Article
- The first-in-Africa ex vivo drug sensitivity testing platform identifies novel drug combinations for South African leukaemia patient cohort.Scientific reports · 2025Article
- Combination of BCL-2 inhibitors and immunotherapy: a promising therapeutic strategy for hematological malignancies.Discover oncology · 2024Review
- Immunophenotyping with (phospho)protein profiling and fluorescent cell barcoding for single-cell signaling analysis and biomarker discovery.NPJ precision oncology · 2024Review
- A tumor microenvironment model of chronic lymphocytic leukemia enables drug sensitivity testing to guide precision medicine.Cell death discovery · 2023Article
- Application of Drug Repurposing-Based Precision Medicine Platform for Leukaemia Patient Treatment.Advances in experimental medicine and biology · 2023Review
- PI3K inhibitors in chronic lymphocytic leukemia: where do we go from here?Haematologica · 2023Review
- Functional Testing to Characterize and Stratify PI3K Inhibitor Responses in Chronic Lymphocytic Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Determining drug dose in the era of targeted therapies: playing it (un)safe?Blood cancer journal · 2022Review
- Functional testing of relapsed chronic lymphocytic leukemia guides precision medicine and maps response and resistance mechanisms. An index case.Haematologica · 2022Article
- Mcl-1 and Bcl-xL levels predict responsiveness to dual MEK/Bcl-2 inhibition in B-cell malignancies.Molecular oncology · 2022Article
- Mutational analysis and protein profiling predict drug sensitivity in multiple myeloma cell lines.Frontiers in oncology · 2022Article
- Computational Pipeline for Rational Drug Combination Screening in Patient-Derived Cells.Methods in molecular biology (Clifton, N.J.) · 2022Article
- PI3K inhibitors are finally coming of age.Nature reviews. Drug discovery · 2021Review
- Extrinsic interactions in the microenvironment in vivo activate an antiapoptotic multidrug-resistant phenotype in CLL.Blood advances · 2021Article
- Overcoming of Microenvironment Protection on Primary Chronic Lymphocytic Leukemia Cells after Treatment with BTK and MDM2 Pharmacological Inhibitors.Current oncology (Toronto, Ont.) · 2021Article
- Overcoming resistance to targeted therapies in chronic lymphocytic leukemia.Blood advances · 2021Article
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, several small molecule drugs were approved for treatment of chronic lymphocytic leukemia (CLL), significantly improving patient management. However, knowledge about how to combine these therapies for optimal effects and what patients will best benefit from them is lacking. Here, we show that drug synergies can be identified by single cell signaling analyses. We investigated the effects of idelalisib, ibrutinib, and venetoclax on 35 protein epitopes by phospho flow in CLL cells. The activity of proteins in the B-cell receptor signalosome and the phosphatidylinositol 3-kinase pathway were altered upon drug exposure. Combined treatment with ibrutinib and venetoclax give promising results in clinical studies and we show that this combination exerted synergistic inhibitory effects on cell signaling and cell viability. Cell viability was monitored by flow cytometry and with independent drug sensitivity screens. Our analyses indicate that the standard dosages of ibrutinib and venetoclax can be lowered without loss of efficacy, potentially reducing drug costs, and toxicities. Observed correlation between signaling and viability indicates that signaling molecules could serve as biomarkers to predict response to therapy. We suggest that phospho flow should be considered as a novel approach for dose and synergy prediction in a precision medicine setting for CLL.
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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.