ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020
A20 and RBX1 Regulate Brentuximab Vedotin Sensitivity in Hodgkin Lymphoma Models.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- A phase II study of brentuximab vedotin in patients with relapsed or refractory Epstein-Barr virus-positive and CD30-positive lymphomas.Haematologica · 2021Trial
- Beyond CD30: Dual-Targeting of Malignant and Regulatory T Cells by Brentuximab Vedotin Remodels the Lymphoma Microenvironment and Overcomes Resistance via BCL2 Inhibition in Mycosis Fungoides.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Overcoming resistance to antibody-drug conjugates: mechanisms and emerging strategies.The oncologist · 2026Review
- Antibody-Drug Conjugates Targeting CD30 in T-Cell Lymphomas: Clinical Progression and Mechanism.Cancers · 2025Review
- Protein ubiquitination in ovarian cancer immunotherapy: The progress and therapeutic strategy.Genes & diseases · 2024Review
- CRISPR technology in human diseases.MedComm · 2024Review
- Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.Molecular cancer · 2024Review
- Applying CRISPR-Cas9 screens to dissect hematological malignancies.Blood advances · 2023Review
- Review
- Current and Emerging Approaches to Study Microenvironmental Interactions and Drug Activity in Classical Hodgkin Lymphoma.Cancers · 2022Review
- Application of CRISPR-Cas9 System to Study Biological Barriers to Drug Delivery.Pharmaceutics · 2022Review
- Review
- Review
- Generation of Antibody-Drug Conjugate Resistant Models.Cancers · 2021Review
- Antibody-drug conjugates for the treatment of lymphoma: clinical advances and latest progress.Journal of hematology & oncology · 2021Review
- Emerging Therapies in Relapsed and Refractory Hodgkin Lymphoma: What Comes Next After Brentuximab Vedotin and PD-1 Inhibition?Current hematologic malignancy reports · 2021Review
- CRISPR/Cas9 for the treatment of haematological diseases: a journey from bacteria to the bedside.British journal of haematology · 2021Review
- Essential role of the linear ubiquitin chain assembly complex and TAK1 kinase in A20 mutant Hodgkin lymphoma.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
purposeFor patients with refractory/relapsed Hodgkin lymphoma (roughly 20% of total cases), few effective therapeutic options exist. Currently, brentuximab vedotin (BV), a drug-conjugated anti-CD30 antibody, is one of the most effective approved therapy agents for these patients. However, many patients do not achieve complete remission and ultimately develop BV-resistant disease, necessitating a more detailed understanding of the molecular circuitry that drives BV sensitivity and the mechanism of BV resistance. EXPERIMENTAL
designHere, we established a ubiquitin regulator-focused CRISPR library screening platform in Hodgkin lymphoma and carried out a drug sensitization screen against BV to identify genes regulating BV treatment sensitivity.
resultsOur CRISPR library screens revealed the ubiquitin-editing enzymes A20 and RBX1 as key molecule effectors that regulate BV sensitivity in Hodgkin lymphoma line L428. A20 negatively regulates NF-κB activity which is required to prevent BV cytotoxicity. In line with these results, the RNA-seq analysis of the BV-resistant single-cell clones demonstrated a consistent upregulation of NF-κB signature genes, as well as the ABC transporter gene ABCB1. Mechanically, NF-κB regulates BV treatment sensitivity through mediating ABCB1 expression. Targeting NF-κB activity synergized well with BV in killing Hodgkin lymphoma cell lines, augmented BV sensitivity, and overcame BV resistance
conclusionsOur identification of this previously unrecognized mechanism provides novel knowledge of possible BV responsiveness and resistance mechanisms in Hodgkin lymphoma, as well as leads to promising hypotheses for the development of therapeutic strategies to overcome BV resistance in this disease.
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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.