ArticleClinical and experimental medicine2020
Inhibition of HSP90 overcomes melphalan resistance through downregulation of Src in multiple myeloma cells.
Article in Clinical and experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- The Prognostic Role of Cyclin D1 in Multiple Myeloma: A Systematic Review and Meta-Analysis.Technology in cancer research & treatmentPooled it
- Potential benefits of combined treatment with Hsp90 inhibitor AUY922 and cisplatin for overcoming drug resistance in nasopharyngeal carcinoma.American journal of cancer research · 2025Article
- KW2478 and Cisplatin Synergistically Anti-colorectal Cancer by Targeting PI3K/AKT/mTOR Pathway.Anti-cancer agents in medicinal chemistry · 2025Article
- Review
- Role of SIRT1 in Chemoresistant Leukemia.International journal of molecular sciences · 2023Review
- Bim downregulation by activation of NF-κB p65, Akt, and ERK1/2 is associated with adriamycin and dexamethasone resistance in multiple myeloma cells.Clinical and experimental medicine · 2023Article
- HSP90β Impedes STUB1-Induced Ubiquitination of YTHDF2 to Drive Sorafenib Resistance in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Simultaneous quantitation of multiple myeloma related dietary metabolites in serum using HILIC-LC-MS/MS.Food & nutrition research · 2023Article
- The potential link between Covid-19 and multiple myeloma: A new saga.Immunity, inflammation and disease · 2022Review
- The HSP90 inhibitor KW-2478 depletes the malignancy of BCR/ABL and overcomes the imatinib-resistance caused by BCR/ABL amplification.Experimental hematology & oncology · 2022Article
- Designing Novel Compounds for the Treatment and Management of RET-Positive Non-Small Cell Lung Cancer-Fragment Based Drug Design Strategy.Molecules (Basel, Switzerland) · 2022Article
- Bioinformatics Analysis of the Key Genes and Pathways in Multiple Myeloma.International journal of general medicine · 2022Article
- Article
- Complex Crystal Structure Determination andFrontiers in cell and developmental biology · 2021Article
- Dasatinib reverses drug resistance by downregulating MDR1 and Survivin in Burkitt lymphoma cells.BMC complementary medicine and therapies · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple myeloma (MM) is the second most common hematologic malignancy. In spite of the development of new therapeutic agents, MM remains incurable due to multidrug resistance (MDR) and the 5-year survival rate is approximately 50%. Thus, further study is needed to investigate the mechanism of MDR and improve MM prognosis. Heat shock protein 90 (HSP90) is a molecular chaperone that is responsible for the stability of a number of client proteins, most of which are involved in tumor progression. Therefore, HSP90 inhibitors represent potential new therapeutic agents for cancer. Furthermore, inhibition of HSP90 leads to degradation of client proteins, overcoming acquired anti-cancer drug resistance. In this study, we assessed the role of HSP90 in MDR using established melphalan-resistant MM cells. We found that expression of HSP90 was higher in melphalan-resistant MM cells than in parent cells and that HSP90 inhibitors KW-2478 and NUV-AUY922 restored drug sensitivity to the level observed in parent cells. Activation of the unfolded protein response is a hallmark of MM, and expression of endoplasmic reticulum stress signaling molecules is reduced in melphalan-resistant cells; however, KW-2478 did not affect endoplasmic reticulum stress signaling. We demonstrated that treatment with KW-2478 decreased expression of Src, a client of HSP90, and suppressed the activity of ERK, Akt, and NF-κB. Our findings indicate that inhibition of HSP90 results in suppression of Src and its downstream effectors, including ERK, Akt, and NF-κB, and therefore that HSP90 inhibitors could be useful for treatment of MDR MM.
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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 OpenQuestion graph.