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Targeting PSMD1 with small interfering RNA (siRNA), delivered via lipid nanoparticles (LNPs), reduced tumor growth in MM cell lines and primary patient samples while sparing normal cells. It also overcame proteasome inhibitor resistance and the protective effects of the bone marrow milieu. In MM xenograft mouse models, PSMD1 siRNA LNPs significantly reduced tumor growth and prolonged survival. In addition, PSMD1 depletion had similar effects on other types of cancer cell lines. These findings position PSMD1 as a critical target in cancer therapy, with broad implications for overcoming drug resistance, improving therapeutic outcomes, and potentially affecting immune responses across various cancers. These findings provide a foundation for the clinical development of PSMD1-targeted therapies in myeloma and other malignancies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025029358","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T18:56:18Z","timestamp":1770144978000},"page":"2344-2357","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":6,"title":["Proteasome subunit PSMD1 is a key therapeutic target in multiple myeloma"],"prefix":"10.1182","volume":"147","author":[{"given":"Ting","family":"Du","sequence":"first","affiliation":[{"name":"1Department of Medical Oncology, LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng","family":"Fang","sequence":"additional","affiliation":[{"name":"1Department of Medical Oncology, LeBow Institute for 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