ArticleCell death & disease2013
Preclinical screening of histone deacetylase inhibitors combined with ABT-737, rhTRAIL/MD5-1 or 5-azacytidine using syngeneic Vk*MYC multiple myeloma.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
21 citing papers in PubMed, 47 citations in OpenAlex.
- A Phase I Clinical Study and In Vivo Findings with PT-112, a Novel Immunogenic Cell Death-Inducing Small Molecule, in Relapsed or Refractory Multiple Myeloma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Targeting the epigenome with advanced delivery strategies for epigenetic modulators.Bioengineering & translational medicine · 2025Review
- Article
- Effect of Zebularine on Apoptotic Pathways in Hepatocellular Carcinoma Cell Lines.International journal of preventive medicine · 2023Article
- PDI inhibitor LTI6426 enhances panobinostat efficacy in preclinical models of multiple myeloma.Cancer chemotherapy and pharmacology · 2022Article
- Cluster Gauss-Newton and CellNOpt Parameter Estimation in a Small Protein Signaling Network of Vorinostat and Bortezomib Pharmacodynamics.The AAPS journal · 2021Article
- Shifting the paradigm in treating multi-factorial diseases: polypharmacological co-inhibitors of HDAC6.RSC medicinal chemistry · 2021Review
- Animal Models of Multiple Myeloma Bone Disease.Frontiers in genetics · 2021Review
- Pan-PIM kinase inhibitors enhance Lenalidomide's anti-myeloma activity via cereblon-IKZF1/3 cascade.Cancer letters · 2019Article
- Immunotherapeutics in Multiple Myeloma: How Can Translational Mouse Models Help?Journal of oncology · 2019Review
- The Use of Murine Models for Studying Mechanistic Insights of Genomic Instability in Multiple Myeloma.Frontiers in genetics · 2019Review
- The Therapeutic Strategy of HDAC6 Inhibitors in Lymphoproliferative Disease.International journal of molecular sciences · 2018Review
- DNMTi/HDACi combined epigenetic targeted treatment induces reprogramming of myeloma cells in the direction of normal plasma cells.British journal of cancer · 2018Article
- Article
- Preclinical animal models of multiple myeloma.BoneKEy reports · 2016Article
- Functional-genetic dissection of HDAC dependencies in mouse lymphoid and myeloid malignancies.Blood · 2015Article
- Immunosurveillance and therapy of multiple myeloma are CD226 dependent.The Journal of clinical investigation · 2015Article
- Selective inhibition of esophageal cancer cells by combination of HDAC inhibitors and Azacytidine.Epigenetics · 2015Article
- The potential of panobinostat as a treatment option in patients with relapsed and refractory multiple myeloma.Therapeutic advances in hematology · 2014Review
- Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
Multiple myeloma (MM) is an incurable malignancy with an unmet need for innovative treatment options. Histone deacetylase inhibitors (HDACi) are a new class of anticancer agent that have demonstrated activity in hematological malignancies. Here, we investigated the efficacy and safety of HDACi (vorinostat, panobinostat, romidepsin) and novel combination therapies using in vitro human MM cell lines and in vivo preclinical screening utilizing syngeneic transplanted Vk*MYC MM. HDACi were combined with ABT-737, which targets the intrinsic apoptosis pathway, recombinant human tumour necrosis factor-related apoptosis-inducing ligand (rhTRAIL/MD5-1), that activates the extrinsic apoptosis pathway or the DNA methyl transferase inhibitor 5-azacytidine. We demonstrate that in vitro cell line-based studies provide some insight into drug activity and combination therapies that synergistically kill MM cells; however, they do not always predict in vivo preclinical efficacy or toxicity. Importantly, utilizing transplanted Vk*MYC MM, we report that panobinostat and 5-azacytidine synergize to prolong the survival of tumor-bearing mice. In contrast, combined HDACi/rhTRAIL-based strategies, while efficacious, demonstrated on-target dose-limiting toxicities that precluded prolonged treatment. Taken together, our studies provide evidence that the transplanted Vk*MYC model of MM is a useful screening tool for anti-MM drugs and should aid in the prioritization of novel drug testing in the clinic.
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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.