ArticleBlood2016
High-content screening identifies kinase inhibitors that overcome venetoclax resistance in activated CLL cells.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 125 citations in OpenAlex.
- Janus kinases restrain chronic lymphocytic leukemia cells in patients on ibrutinib: Results of a phase II trial.Cancer medicine · 2021Trial
- DR5/WDR12 balances p65 stability promoting sunitinib resistance in renal cell carcinoma.Cell death and differentiation · 2026Article
- FOXM1 induces therapy resistance and inhibits apoptosis in a variety of human cancers.Cell death & disease · 2026Review
- High-content imaging of primary chronic lymphocytic leukemia cells predicts patient cohorts with distinct cellular drug responses.iScience · 2025Article
- Synergistic effect of cold gas plasma and experimental drug exposure exhibits skin cancer toxicity in vitro and in vivo.Journal of advanced research · 2024Article
- BCL-2 inhibitors in hematological malignancies: biomarkers that predict response and management strategies.Frontiers in oncology · 2024Review
- Co-targeting BCL-XL and BCL-2 by PROTAC 753B eliminates leukemia cells and enhances efficacy of chemotherapy by targeting senescent cells.Haematologica · 2023Article
- PP2A modulation overcomes multidrug resistance in chronic lymphocytic leukemia via mPTP-dependent apoptosis.The Journal of clinical investigation · 2023Article
- Human nuclear hormone receptor activity contributes to malaria parasite liver stage development.Cell chemical biology · 2023Article
- NF-kB and the CLL microenvironment.Frontiers in oncology · 2023Review
- Paradoxical activation of chronic lymphocytic leukemia cells by ruxolitinibFrontiers in oncology · 2023Article
- Venetoclax resistance induced by activated T cells can be counteracted by sphingosine kinase inhibitors in chronic lymphocytic leukemia.Frontiers in oncology · 2023Article
- Targeting the immune microenvironment in mantle cell lymphoma: implications for current and emerging therapies.Leukemia & lymphoma · 2022Review
- Tipping the balance: toward rational combination therapies to overcome venetoclax resistance in mantle cell lymphoma.Leukemia · 2022Review
- Drug-microenvironment perturbations reveal resistance mechanisms and prognostic subgroups in CLL.Molecular systems biology · 2022Article
- In Vitro and In Vivo Models of CLL-T Cell Interactions: Implications for Drug Testing.Cancers · 2022Review
- Efficacy and specificity of inhibitors of BCL-2 family protein interactions assessed by affinity measurements in live cells.Science advances · 2022Article
- Venetoclax-resistant CLL cells show a highly activated and proliferative phenotype.Cancer immunology, immunotherapy : CII · 2022Article
- Targeting HNRNPU to overcome cisplatin resistance in bladder cancer.Molecular cancer · 2022Article
- Mechanisms of venetoclax resistance and solutions.Frontiers in oncology · 2022Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Novel agents such as the Bcl-2 inhibitor venetoclax (ABT-199) are changing treatment paradigms for chronic lymphocytic leukemia (CLL) but important problems remain. Although some patients exhibit deep and durable responses to venetoclax as a single agent, other patients harbor subpopulations of resistant leukemia cells that mediate disease recurrence. One hypothesis for the origin of resistance to venetoclax is by kinase-mediated survival signals encountered in proliferation centers that may be unique for individual patients. An in vitro microenvironment model was developed with primary CLL cells that could be incorporated into an automated high-content microscopy-based screen of kinase inhibitors (KIs) to identify agents that may improve venetoclax therapy in a personalized manner. Marked interpatient variability was noted for which KIs were effective; nevertheless, sunitinib was identified as the most common clinically available KI effective in overcoming venetoclax resistance. Examination of the underlying mechanisms indicated that venetoclax resistance may be induced by microenvironmental signals that upregulate antiapoptotic Bcl-xl, Mcl-1, and A1, which can be counteracted more efficiently by sunitinib than by ibrutinib or idelalisib. Although patient-specific drug responses are common, for many patients, combination therapy with sunitinib may significantly improve the therapeutic efficacy of venetoclax.
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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.