ArticleOncotarget2016
Ibrutinib synergizes with poly(ADP-ribose) glycohydrolase inhibitors to induce cell death in AML cells via a BTK-independent mechanism.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Impact of physiological media on acute myeloid leukemia bioenergetics and cell proliferation.Cancer & metabolism · 2025Article
- The PKM2 inhibitor shikonin enhances piceatannol-induced apoptosis of glyoxalase I-dependent cancer cells.Genes to cells : devoted to molecular & cellular mechanisms · 2024Article
- A Dual Anti-Inflammatory and Anti-Proliferative 3-Styrylchromone Derivative Synergistically Enhances the Anti-Cancer Effects of DNA-Damaging Agents on Colon Cancer Cells by Targeting HMGB1-RAGE-ERK1/2 Signaling.International journal of molecular sciences · 2022Article
- Ethacridine inhibits SARS-CoV-2 by inactivating viral particles.PLoS pathogens · 2021Article
- β-Thujaplicin Enhances TRAIL-Induced Apoptosis via the Dual Effects of XIAP Inhibition and Degradation in NCI-H460 Human Lung Cancer Cells.Medicines (Basel, Switzerland) · 2021Article
- Poly (ADP) Ribose Glycohydrolase Can Be Effectively Targeted in Pancreatic Cancer.Cancer research · 2019Article
- Multiple Roles for Mono- and Poly(ADP-Ribose) in Regulating Stress Responses.Trends in genetics : TIG · 2019Review
- Role of Bruton's tyrosine kinase in B cells and malignancies.Molecular cancer · 2018Review
- Call for Action: Invasive Fungal Infections Associated With Ibrutinib and Other Small Molecule Kinase Inhibitors Targeting Immune Signaling Pathways.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Article
- The combination effect of homoharringtonine and ibrutinib on FLT3-ITD mutant acute myeloid leukemia.Oncotarget · 2017Article
- Erlotinib synergizes with the poly(ADP-ribose) glycohydrolase inhibitor ethacridine in acute myeloid leukemia cells.Haematologica · 2016Article
- A Subset of Patients with Acute Myeloid Leukemia Has Leukemia Cells Characterized by Chemokine Responsiveness and Altered Expression of Transcriptional as well as Angiogenic Regulators.Frontiers in immunology · 2016Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Targeting Bruton's tyrosine kinase (BTK) with the small molecule BTK inhibitor ibrutinib has significantly improved patient outcomes in several B-cell malignancies, with minimal toxicity. Given the reported expression and constitutive activation of BTK in acute myeloid leukemia (AML) cells, there has been recent interest in investigating the anti-AML activity of ibrutinib. We noted that ibrutinib had limited single-agent toxicity in a panel of AML cell lines and primary AML samples, and therefore sought to identify ibrutinib-sensitizing drugs. Using a high-throughput combination chemical screen, we identified that the poly(ADP-ribose) glycohydrolase (PARG) inhibitor ethacridine lactate synergized with ibrutinib in TEX and OCI-AML2 leukemia cell lines. The combination of ibrutinib and ethacridine induced a synergistic increase in reactive oxygen species that was functionally important to explain the observed cell death. Interestingly, synergistic cytotoxicity of ibrutinib and ethacridine was independent of the inhibitory effect of ibrutinib against BTK, as knockdown of BTK did not sensitize TEX and OCI-AML2 cells to ethacridine treatment. Thus, our findings indicate that ibrutinib may have a BTK-independent role in AML and that PARG inhibitors may have utility as part of a combination therapy for this disease.
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Registered trials
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