{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:14:48Z","timestamp":1790388888752,"version":"4.1.0"},"reference-count":117,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by high metabolic activity, chronic endoplasmic reticulum stress, and persistent redox imbalance. Excessive immunoglobulin synthesis and adaptation to the hypoxic bone marrow microenvironment lead to sustained production of reactive oxygen species (ROS). Their excessive accumulation promotes genomic instability, disease progression, osteolytic bone disease, and resistance to therapy. Paradoxically, MM cells adapt to oxidative stress by activating antioxidant and metabolic defense mechanisms, including Nuclear factor erythroid 2-related factor 2 (NRF2)- and Heme Oxygenase 1 (HMOX1)-dependent pathways, metabolic reprogramming, and overexpression of ROS-scavenging enzymes such as peroxiredoxin 6 (PRDX6), allowing survival at the threshold of oxidative toxicity. Evidence indicates that biomarkers of oxidative stress\u2014such as lipid and protein oxidation products, antioxidant enzyme activity, and the Oxidative Stress Score\u2014correlate with disease stage, prognosis, and treatment response. Redox-modulating therapeutic strategies, including pharmacological ROS induction, inhibition of antioxidant defenses, and the use of natural pro-oxidant compounds, are emerging as promising adjuncts to standard MM therapies. Recent studies also highlight the gut microbiota as an indirect regulator of oxidative balance, immune modulation, and metabolic homeostasis in MM. This review summarizes current knowledge on oxidative stress in multiple myeloma, emphasizing its role in pathogenesis, drug resistance, biomarker development, and emerging therapeutic and supportive strategies.<\/jats:p>","DOI":"10.3390\/ijms27073001","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T13:36:40Z","timestamp":1774532200000},"page":"3001","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Oxidative Stress in Multiple Myeloma: Pathogenic Mechanisms, Biomarkers, and Redox-Targeted Therapeutic Strategies"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5197-4281","authenticated-orcid":false,"given":"Rafa\u0142","family":"Bilski","sequence":"first","affiliation":[{"name":"Department of Medical Biology and Biochemistry, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, M. Kar\u0142owicz Str. 24, 85-092 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1542-0879","authenticated-orcid":false,"given":"Daria","family":"Kupczyk","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Biochemistry, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, M. Kar\u0142owicz Str. 24, 85-092 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Kaczorowska-Bilska","sequence":"additional","affiliation":[{"name":"Clinic of Hematology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, K. Ujejskiego Str. 75. 85-168 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3951-9005","authenticated-orcid":false,"given":"Halina","family":"Tkaczenko","sequence":"additional","affiliation":[{"name":"Institute of Biology, Pomeranian University in S\u0142upsk, Arciszewski Str. 22b, 76-200 Slupsk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4669-1092","authenticated-orcid":false,"given":"Natalia","family":"Kurhaluk","sequence":"additional","affiliation":[{"name":"Institute of Biology, Pomeranian University in S\u0142upsk, Arciszewski Str. 22b, 76-200 Slupsk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0081-0412","authenticated-orcid":false,"given":"Tomasz","family":"Kosmalski","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, Jurasza Str. 2. 85-089 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4137-2981","authenticated-orcid":false,"given":"Artur","family":"S\u0142omka","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, National Medical Institute of the Ministry of Interior and Administration, 02-507 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5853-4214","authenticated-orcid":false,"given":"Renata","family":"Studzi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru\u0144, Jurasza Str. 2. 85-089 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kul, A., and Kurt, B.O. 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