ABSTRACT Despite recent advances in treatment, multiple myeloma (MM) remains an incurable malignancy. By using _in vitro_, _ex vivo_ and _in vivo_ approaches, we have identified here that

lipid rafts constitute a new target in MM. We have found that the phospholipid ether edelfosine targets and accumulates in MM cell membrane rafts, inducing apoptosis through co-clustering of

rafts and death receptors. Raft disruption by cholesterol depletion inhibited drug uptake by tumor cells as well as cell killing. Cholesterol replenishment restored MM cell ability to take

up edelfosine and to undergo drug-induced apoptosis. Ceramide addition displaced cholesterol from rafts, and inhibited edelfosine-induced apoptosis. In an MM animal model, edelfosine oral

clinical evaluation of edelfosine and for this raft-targeted therapy to improve patient outcome in MM. Our data reveal cholesterol-containing lipid rafts as a novel and efficient therapeutic

target in MM, opening a new avenue in cancer treatment. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS

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institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS ACSL4-MEDIATED LIPID RAFTS PREVENT MEMBRANE RUPTURE AND INHIBIT IMMUNOGENIC CELL

DEATH IN MELANOMA Article Open access 29 September 2024 SELECTIVE MCL-1 INHIBITOR ABBV-467 IS EFFICACIOUS IN TUMOR MODELS BUT IS ASSOCIATED WITH CARDIAC TROPONIN INCREASES IN PATIENTS

Article Open access 25 October 2023 SUPPRESSION OF MULTIPLE MYELOMA BY MITOCHONDRIAL TARGETING Article Open access 12 March 2021 REFERENCES * Auer J, Berent R, Weber T, Eber B . (2002).

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xenografts. _J Clin Invest_ 115: 959–968. Article  CAS  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS This work was supported by grants from Ministerio de

Ciencia e Innovación (SAF2007-61261, SAF2008-02251, PCT-090100-2007-27, RD06/0020/1037 from Red Temática de Investigación Cooperativa en Cáncer, Instituto de Salud Carlos III), Fondo de

Investigación Sanitaria and European Commission (FIS-FEDER 06/0813, PS09/01915), Junta de Castilla y León (GR15-Experimental Therapeutics and Translational Oncology Program, and Biomedicine

Project 2009) and Caja Navarra Foundation, Department of Health of the Navarra Government (‘Ortiz de Landázuri, 2009’ project). CG is supported by the Ramón y Cajal Program from the

Ministerio de Ciencia e Innovación of Spain. AEHdM is supported by a research grant (BF106.37) from the Department of Education of the Basque Government. AUTHOR INFORMATION AUTHORS AND

AFFILIATIONS * Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, CSIC-Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain F

Mollinedo, J de la Iglesia-Vicente, C Gajate & J A Villa-Pulgarin * Unidad de Investigación, Hospital Universitario de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain C Gajate *

Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Navarra, Pamplona, Spain A Estella-Hermoso de Mendoza & M J Blanco-Prieto * Servicio de

Farmacología Clínica, Clínica Universitaria, Pamplona, Spain M A Campanero Authors * F Mollinedo View author publications You can also search for this author inPubMed Google Scholar * J de

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Google Scholar * A Estella-Hermoso de Mendoza View author publications You can also search for this author inPubMed Google Scholar * J A Villa-Pulgarin View author publications You can also

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publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHORS Correspondence to F Mollinedo or C Gajate. ETHICS DECLARATIONS COMPETING INTERESTS The authors

declare no conflict of interest. ADDITIONAL INFORMATION Supplementary Information accompanies the paper on the Oncogene website SUPPLEMENTARY INFORMATION SUPPLEMENTARY DATA (PDF 71 KB)

RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Mollinedo, F., de la Iglesia-Vicente, J., Gajate, C. _et al._ Lipid raft-targeted therapy in multiple

myeloma. _Oncogene_ 29, 3748–3757 (2010). https://doi.org/10.1038/onc.2010.131 Download citation * Received: 23 October 2009 * Revised: 12 January 2010 * Accepted: 07 February 2010 *

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lipid raft * cholesterol * phospholipid ether * edelfosine * apoptosis * MM