ArticleBlood cancer journal2012
Anti-tumor activity against multiple myeloma by combination of KW-2478, an Hsp90 inhibitor, with bortezomib.
Article in Blood cancer journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- A phase I/II study of KW-2478, an Hsp90 inhibitor, in combination with bortezomib in patients with relapsed/refractory multiple myeloma.British journal of cancer · 2017Trial
- Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.Haematologica · 2026Article
- Exogenous Heat Shock Proteins in Oncology: Biological Roles and Clinical Implications.Cancers · 2026Review
- Targeting the proteasome in cancer therapy: development and future opportunities in natural products.Frontiers in pharmacology · 2026Review
- Impact of proteostasis workload on sensitivity to proteasome inhibitors in multiple myeloma.Clinical and experimental medicine · 2025Review
- Overcoming cancer drug resistance through small-molecule targeting of HSP90 and HSP70.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Chemo-RaST with bortezomib inhibits multiple myeloma relapse.Theranostics · 2025Article
- Unrevealed roles of extracellular enolase‑1 (ENO1) in promoting glycolysis and pro‑cancer activities in multiple myeloma via hypoxia‑inducible factor 1α.Oncology reports · 2023Article
- HSP90 inhibitors and cancer: Prospects for use in targeted therapies (Review).Oncology reports · 2023Review
- Review
- A Drug Screening Reveals Minocycline Hydrochloride as a Therapeutic Option to Prevent Breast Cancer Cells Extravasation across the Blood-Brain Barrier.Biomedicines · 2022Article
- Drug resistance in multiple myeloma: Soldiers and weapons in the bone marrow niche.Frontiers in oncology · 2022Review
- Inhibitor Combinations Reveal Wiring of the Proteostasis Network in Prostate Cancer Cells.Journal of medicinal chemistry · 2021Article
- Preclinical and Early Clinical Development of PTC596, a Novel Small-Molecule Tubulin-Binding Agent.Molecular cancer therapeutics · 2021Article
- In vivo quantitative assessment of therapeutic response to bortezomib therapy in disseminated animal models of multiple myeloma with [EJNMMI research · 2021Article
- The Landscape of Signaling Pathways and Proteasome Inhibitors Combinations in Multiple Myeloma.Cancers · 2021Review
- Overcoming drug resistance by targeting protein homeostasis in multiple myeloma.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Design and Synthesis of Fungal-Selective Resorcylate Aminopyrazole Hsp90 Inhibitors.Journal of medicinal chemistry · 2020Article
- Review
- Inhibition of HSP90 overcomes melphalan resistance through downregulation of Src in multiple myeloma cells.Clinical and experimental medicine · 2020Article
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heat shock protein 90 (Hsp90) is a promising target for anti-tumor therapy. We previously reported the anti-tumor activity of a novel Hsp90 inhibitor, KW-2478, in multiple myeloma (MM) as a single agent. In this study, we examined the combinational effect of KW-2478 and bortezomib, a proteasome inhibitor, in vitro and in vivo. In vitro, KW-2478 enhanced bortezomib-induced cell growth inhibition, both in MM cell lines and primary patient MM cells. The combination of KW-2478 and bortezomib also induced caspase activation in MM cell lines. Interestingly, the combination synergistically enhanced the expression of Hsp70B, a homolog of Hsp70, in human MM cells and peripheral blood mononuclear cells, indicating Hsp70B could be a surrogate biomarker for the combination of Hsp90 and proteasome inhibitors. In vivo, the combination of KW-2478 with bortezomib showed synergistic anti-tumor activity without significant body weight loss in a subcutaneously inoculated human myeloma model. Furthermore, the combination also showed synergistic reduction of tumor burden in bone marrow in an orthotopic myeloma model. Our results strongly suggest that combination of KW-2478 with bortezomib could exhibit enhanced anti-tumor activity against human myeloma.
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