ArticleLeukemia2020
Survey of ex vivo drug combination effects in chronic lymphocytic leukemia reveals synergistic drug effects and genetic dependencies.
Article in Leukemia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Article
- Roles of myeloperoxidase and the AMPK/PI3K/AKT/eNOS pathway in osimertinib-induced cardiotoxicity: multilevel evidence from disequilibrium analysis, network pharmacology, mendelian randomization, and animal experiments.Frontiers in pharmacology · 2026Article
- Double Strike in Chronic Lymphocytic Leukemia-The Combination of BTK and BCL2 Inhibitors in Actual and Future Clinical Practice.International journal of molecular sciences · 2025Review
- The first-in-Africa ex vivo drug sensitivity testing platform identifies novel drug combinations for South African leukaemia patient cohort.Scientific reports · 2025Article
- BCL-2 dependence is a favorable predictive marker of response to therapy for chronic lymphocytic leukemia.Molecular cancer · 2025Article
- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
- Lymphoma and Leukemia Cell Vulnerabilities and Resistance Identified by Compound Library Screens.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Disrupting pro-survival and inflammatory pathways with dimethyl fumarate sensitizes chronic lymphocytic leukemia to cell death.Cell death & disease · 2024Article
- A tumor microenvironment model of chronic lymphocytic leukemia enables drug sensitivity testing to guide precision medicine.Cell death discovery · 2023Article
- Ex vivo drug sensitivity screening in multiple myeloma identifies drug combinations that act synergistically.Molecular oncology · 2022Article
- Mutational analysis and protein profiling predict drug sensitivity in multiple myeloma cell lines.Frontiers in oncology · 2022Article
- Targeted and cellular therapies in lymphoma: Mechanisms of escape and innovative strategies.Frontiers in oncology · 2022Review
- DrugComb update: a more comprehensive drug sensitivity data repository and analysis portal.Nucleic acids research · 2021Article
- Overcoming resistance to targeted therapies in chronic lymphocytic leukemia.Blood advances · 2021Article
- Genetic and Non-Genetic Mechanisms of Resistance to BCR Signaling Inhibitors in B Cell Malignancies.Frontiers in oncology · 2020Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Drug combinations that target critical pathways are a mainstay of cancer care. To improve current approaches to combination treatment of chronic lymphocytic leukemia (CLL) and gain insights into the underlying biology, we studied the effect of 352 drug combination pairs in multiple concentrations by analysing ex vivo drug response of 52 primary CLL samples, which were characterized by "omics" profiling. Known synergistic interactions were confirmed for B-cell receptor (BCR) inhibitors with Bcl-2 inhibitors and with chemotherapeutic drugs, suggesting that this approach can identify clinically useful combinations. Moreover, we uncovered synergistic interactions between BCR inhibitors and afatinib, which we attribute to BCR activation by afatinib through BLK upstream of BTK and PI3K. Combinations of multiple inhibitors of BCR components (e.g., BTK, PI3K, SYK) had effects similar to the single agents. While PI3K and BTK inhibitors produced overall similar effects in combinations with other drugs, we uncovered a larger response heterogeneity of combinations including PI3K inhibitors, predominantly in CLL with mutated IGHV, which we attribute to the target's position within the BCR-signaling pathway. Taken together, our study shows that drug combination effects can be effectively queried in primary cancer cells, which could aid discovery, triage and clinical development of drug combinations.
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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.