ArticleThe Journal of clinical investigation2023
Cotargeting of BTK and MALT1 overcomes resistance to BTK inhibitors in mantle cell lymphoma.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Genetic subtype-guided immunochemotherapy in relapsed and refractory diffuse large B cell lymphoma: a phase 2 investigator-initiated nonrandomized clinical trial (GUIDANCE-06).Signal transduction and targeted therapy · 2025Trial
- High-Dose Methotrexate, Ibrutinib, and Temozolomide in the Treatment of Newly Diagnosed Primary CNS Lymphoma: A Multicenter, Prospective Phase II Study.Blood cancer discovery · 2025Trial
- Effect of MALT1 inhibition by MI‑2 on the microglial phenotype switch, inflammatory cytokine secretion, neuronal loss and oxidative stress in Alzheimer's disease.International journal of molecular medicine · 2026Article
- Bruton's Tyrosine Kinase Inhibitors: Mechanisms, Efficacy, Toxicities and Applications for the Treatment of Human Diseases.MedComm · 2026Review
- Mechanisms of resistance to BTK inhibitors in B cell malignancies and emerging targeted strategies.Molecular therapy. Oncology · 2026Review
- MOF promotes venous thromboembolism in lung cancer by activating the YBX1-MALT1-NF-κB-PAI-1 axis, possibly through histone crotonylation.The Journal of biological chemistry · 2026Article
- Cyclin-Dependent Kinase-9 and Oxidative Phosphorylation Inhibition Overcomes Ibrutinib Resistance in Mantle Cell Lymphoma.Cancer research communications · 2026Article
- The double-edged sword of tumor-targeted treatment: the influence of targeted therapy on the heart.Translational cancer research · 2026Review
- Targeting signaling pathways in lymphoma: From molecular mechanisms to clinical breakthroughs.Chinese medical journal · 2026Review
- MALT1 inhibition by MI‑2 suppresses epithelial‑to‑mesenchymal transition and fibrosis by inactivating the NF‑κB pathway in high glucose‑treated HK‑2 cells.Molecular medicine reports · 2026Article
- SOX11 modulates BCR signaling through the PAX5/CD19 axis for therapeutic targeting in BTK-resistant mantle cell lymphoma.Blood advances · 2025Article
- The Precision Revolution in Hematologic Malignancies: A Decade of Transformative Immunotherapies and Targeted Agents.Journal of clinical medicine · 2025Review
- B-cell receptor signaling and microenvironment crosstalk in mantle cell lymphoma.Cell communication and signaling : CCS · 2025Review
- Bruton's tyrosine kinase inhibition re-sensitizes multidrug-resistant DLBCL tumors driven by BCL10 gain-of-function mutants to venetoclax.Blood cancer journal · 2025Article
- Case report: A panorama gene profile of ovarian cancer metastasized to axillary lymph node.Frontiers in immunology · 2025Article
- Article
- Targeted protein degradation: advances in drug discovery and clinical practice.Signal transduction and targeted therapy · 2024Review
- Review
- Impact of PIK3CA gain and PTEN loss on mantle cell lymphoma biology and sensitivity to targeted therapies.Blood advances · 2024Article
- Article
Corrections and comments
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Authors and funding
21 authors at 2 institutions in 1 country.
Funding
Abstract
Bruton's tyrosine kinase (BTK) is a proven target in mantle cell lymphoma (MCL), an aggressive subtype of non-Hodgkin lymphoma. However, resistance to BTK inhibitors is a major clinical challenge. We here report that MALT1 is one of the top overexpressed genes in ibrutinib-resistant MCL cells, while expression of CARD11, which is upstream of MALT1, is decreased. MALT1 genetic knockout or inhibition produced dramatic defects in MCL cell growth regardless of ibrutinib sensitivity. Conversely, CARD11-knockout cells showed antitumor effects only in ibrutinib-sensitive cells, suggesting that MALT1 overexpression could drive ibrutinib resistance via bypassing BTK/CARD11 signaling. Additionally, BTK knockdown and MALT1 knockout markedly impaired MCL tumor migration and dissemination, and MALT1 pharmacological inhibition decreased MCL cell viability, adhesion, and migration by suppressing NF-κB, PI3K/AKT/mTOR, and integrin signaling. Importantly, cotargeting MALT1 with safimaltib and BTK with pirtobrutinib induced potent anti-MCL activity in ibrutinib-resistant MCL cell lines and patient-derived xenografts. Therefore, we conclude that MALT1 overexpression associates with resistance to BTK inhibitors in MCL, targeting abnormal MALT1 activity could be a promising therapeutic strategy to overcome BTK inhibitor resistance, and cotargeting of MALT1 and BTK should improve MCL treatment efficacy and durability as well as patient outcomes.
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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.