ArticleProceedings of the National Academy of Sciences of the United States of America2016
Augmented efficacy of brentuximab vedotin combined with ruxolitinib and/or Navitoclax in a murine model of human Hodgkin's lymphoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 44 citations in OpenAlex.
- A phase II study of the oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma.Haematologica · 2018Trial
- Overcoming resistance to antibody-drug conjugates: mechanisms and emerging strategies.The oncologist · 2026Review
- Identification of basement membrane-based prognostic signature and potential therapeutic drugs in hepatocellular carcinoma.Translational cancer research · 2025Article
- Therapeutic potential of brentuximab vedotin in breast cancer and lymphoma via targeted apoptosis and gene regulation.Scientific reports · 2025Article
- DCLRE1B as a novel prognostic biomarker associated with immune infiltration: a pancancer analysis.Scientific reports · 2024Article
- Antineoplastic Drug Synergy of Artesunate with Navitoclax in Models of High-Grade Serous Ovarian Cancer.Cancers · 2024Article
- JAK/STAT blockade reverses the malignant phenotype of Hodgkin and Reed-Sternberg cells.Blood advances · 2023Article
- CellMinerCDB: NCATS Is a Web-Based Portal Integrating Public Cancer Cell Line Databases for Pharmacogenomic Explorations.Cancer research · 2023Article
- Therapeutic efficacy of a MMAE-based anti-DR5 drug conjugate Oba01 in preclinical models of pancreatic cancer.Cell death & disease · 2023Article
- Navitoclax Most Promising BH3 Mimetic for Combination Therapy in Hodgkin Lymphoma.International journal of molecular sciences · 2022Article
- Review
- Chemical composition and pharmacological bio-efficacy ofSaudi journal of biological sciences · 2021Article
- Xenograft models for pediatric cancer therapies.Faculty reviews · 2021Review
- Overcoming malignant cell-based mechanisms of resistance to immune checkpoint blockade antibodies.Seminars in cancer biology · 2020Review
- Multi-Omics Investigation of Innate Navitoclax Resistance in Triple-Negative Breast Cancer Cells.Cancers · 2020Article
- Is There a Role for Dual PI3K/mTOR Inhibitors for Patients Affected with Lymphoma?International journal of molecular sciences · 2020Review
- STAT3 Activation and Oncogenesis in Lymphoma.Cancers · 2019Review
- Therapeutic strategies for diffuse midline glioma from high-throughput combination drug screening.Science translational medicine · 2019Article
- Immune and Inflammatory Cells of the Tumor Microenvironment Represent Novel Therapeutic Targets in Classical Hodgkin Lymphoma.International journal of molecular sciences · 2019Review
- CD28 Homolog Is a Strong Activator of Natural Killer Cells for Lysis of B7H7Cancer immunology research · 2019Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Despite relative success of therapy for Hodgkin's lymphoma (HL), novel therapeutic agents are needed for patients with refractory or relapsed disease. Recently, anti-PD1 immunotherapy or treatment with the anti-CD30 toxin conjugate brentuximab vedotin (BV) have been associated with remissions; however, the median responses of complete responses (CRs) with the latter were only 6.7 mo. To obtain curative therapy, other effective agents, based on HL biology, would have to be given in combination with BV. Hodgkin's Reed-Sternberg (HRS) cells secrete cytokines including IL-6 and -13, leading to constitutive activation of JAK/STAT signaling. In the present study the JAK1/2 inhibitor ruxolitinib reduced phosphorylation of STAT3 and STAT6 and expression of c-Myc in the HL cell line HDLM-2. These changes were enhanced when, on the basis of a matrix screen of drug combinations, ruxolitinib was combined with the Bcl-2/Bcl-xL inhibitor Navitoclax. The combination augmented expression of Bik, Puma, and Bax, and attenuated Bcl-xL expression and the phosphorylation of Bad. The use of the two-agent combination of either ruxolitinib or Navitoclax with BV or the three-agent combination strongly activated Bax and increased activities of cytochrome c and caspase-9 and -3 that, in turn, led to cleavage of poly(ADP ribose) polymerase and Mcl-1. Either ruxolitinib combined with Navitoclax or BV alone prolonged survival but did not cure HDLM-2 tumor-bearing mice, whereas BV combined with ruxolitinib and/or with Navitoclax resulted in a sustained, complete elimination of the HDLM-2 HL. These studies provide scientific support for a clinical trial to evaluate BV combined with ruxolitinib in select patients with HL.
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