The instrumental role of lipids in governing the sensitivity of multiple myeloma to ferroptosis

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Habib, Ali
Best, Oliver G
Toomes, Charlotte E
Wallington-Gates, Craig T
Griffith University Author(s)
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2025
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Multiple myeloma (MM) is a malignancy characterised by the uncontrolled proliferation of clonal plasma cells, primarily within the bone marrow, and is still considered incurable. A significant proportion of patients relapse with drug-refractory disease, necessitating the development of novel therapeutic approaches. Ferroptosis is a recently-characterised form of non-apoptotic programmed cell death, linked to phospholipid peroxidation, that represents a promising approach for the treatment of MM and other cancers, that are refractory to more conventional apoptosis-inducing regimens. A better understanding of the relationship between cellular lipid composition and ferroptosis sensitivity is key to harnessing this form of programmed cell death as a therapeutic approach. In addition to the cellular proportions of phospholipids containing poly- and monounsaturated fatty acids, studies to date indicate that cholesterol levels impact not only the onset and progression of haematological malignancies but also the sensitivity of a variety of different cancers to ferroptosis. Therefore, manipulating the uptake and metabolism of lipids, including glycerophospholipids and cholesterol, may be an effective means of sensitising MM cells to ferroptosis. Findings from the limited number of studies concerning ferroptosis in MM and compelling evidence from other malignancies, provide a strong rationale for further investigation of ferroptosis as a novel therapeutic approach for MM.

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Discover Oncology

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16

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© Crown 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Habib, A; Best, OG; Toomes, CE; Wallington-Gates, CT, The instrumental role of lipids in governing the sensitivity of multiple myeloma to ferroptosis, Discover Oncology, 2025, 16, pp. 1612

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