Ortiz Ruiz, AlejandraRuiz Heredia, YaniraMorales, María LuzAguilar Garrido, PedroGarcía Ortiz, AlmudenaValeri Lozano, AntonioBárcena Asensio, María CarmenGarcía Martín, Rosa MaríaGarrido, VanesaMoreno Gutiérrez, LauraGimenez, AliciaNavarro Aguadero, Miguel ÁngelVelasco Estévez, MaríaLospitao, EvaCedena Romero, M. TeresaBarrio, SantiagoMartínez López, JoaquínLinares Gómez, MaríaGallardo, Miguel2023-06-172023-06-172021-04-01Ortiz-Ruiz A, Ruiz-Heredia Y, Morales ML, Aguilar-Garrido P, García-Ortiz A, Valeri A, et al. Myc-Related Mitochondrial Activity as a Novel Target for Multiple Myeloma. Cancers 2021;13:1662. https://doi.org/10.3390/cancers13071662.2072-669410.3390/cancers13071662https://hdl.handle.net/20.500.14352/6886This work was funded by project PI 18/00295, PI18/01519 and CP19/00140 from the Insti- tuto de Salud Carlos III (Ministry of Economy, Industry and Competitiveness) and cofunded by the Eu- ropean Regional Development Fund, CRIS contra el Cancer Foundation, AECC (INVES19015GALL) and Madri+d from Comunidad de Madrid YEI (PEJD-2017-PRE/BMD-4835 and PEJD-2019-POST/ BMD-14505) and approved by the Ethics Committee of our Institution.Mitochondria are involved in the development and acquisition of a malignant phenotype in hematological cancers. Recently, their role in the pathogenesis of multiple myeloma (MM) has been suggested to be therapeutically explored. MYC is a master regulator of b-cell malignancies such as multiple myeloma, and its activation is known to deregulate mitochondrial function. We investigated the impact of mitochondrial activity on the distinct entities of the disease and tested the efficacy of the mitochondrial inhibitor, tigecycline, to overcome MM proliferation. COXII expression, COX activity, mitochondrial mass, and mitochondrial membrane potential demonstrated a progressive increase of mitochondrial features as the disease progresses. In vitro and in vivo therapeutic targeting using the mitochondrial inhibitor tigecycline showed promising efficacy and cytotoxicity in monotherapy and combination with the MM frontline treatment bortezomib. Overall, our findings demonstrate how mitochondrial activity emerges in MM transformation and disease progression and the efficacy of therapies targeting these novel vulnerabilities.engAtribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/journal articlehttps://doi.org/10.3390/cancers13071662https://www.mdpi.com/2072-6694/13/7/1662/htmopen accessMultiple myelomaMitochondriaTigecyclineMYCHematologíaOncologíaBiología celular (Biología)3205.04 Hematología3201.01 Oncología2407 Biología Celular