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Título : Inhibition of Integrin aVb3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma
Autor : Cayrol, María Florencia 
Revuelta, Maria V. 
Debernardi, Maria Mercedes 
Paulazo, Maria Alejandra 
Phillip, Jude M. 
Zamponi, Nahuel 
Sterle, Helena Andrea 
Díaz Flaqué, María Celeste 
Magro, Cynthia 
Marullo, Rossella 
Mulvey, Erin 
Ruan, Jia 
Cremaschi, Graciela A. 
Cerchietti, Leandro 
Palabras clave : INMUNOLOGIALINFOMA DE CÉLULAS TBEXAROTENO
Fecha de publicación : 2022
Editorial : American Association for Cancer Research
Cita : Cayrol, M. F. et al. Inhibition of Integrin aVb3 Signaling Improves the Antineoplastic Effect of Bexarotene in Cutaneous T-Cell Lymphoma [en línea]. Molecular cancer therapeutics, 2022, 21 (9). doi: 10.1158/1535-7163.MCT-22-0093. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/15399
Resumen : Abstract: Bexarotene is a specific retinoid X receptor agonist that has been used for the treatment of cutaneous T-cell lymphoma (CTCL). Because bexarotene causes hypothyroidism, it requires the administration of levothyroxine. However, levothyroxine, in addition to its ubiquitous nuclear receptors, can activate the aVb3 integrin that is overexpressed in CTCL, potentially interfering the antineoplastic effect of bexarotene. We thus investigated the biological effect of levothyroxine in relation to bexarotene treatment. Although in isolated CTCL cells levothyroxine decreased, in an aVb3-dependent manner, the antineoplastic effect of bexarotene, levothyroxine supplementation in preclinical models was necessary to avoid suppression of lymphoma immunity. Accordingly, selective genetic and pharmacologic inhibition of integrin aVb3 improved the antineoplastic effect of bexarotene plus levothyroxine replacement while maintaining lymphoma immunity. Our results provide a mechanistic rationale for clinical testing of integrin aVb3 inhibitors as part of CTCL regimens based on bexarotene administration.
URI : https://repositorio.uca.edu.ar/handle/123456789/15399
ISSN : 1538-8514 (online)
1535-7163 (impreso)
Disciplina: MEDICINA
DOI: 10.1158/1535-7163.MCT-22-0093
Derechos: Acceso restringido
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