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dc.contributor.authorMohlin, Sofie
dc.contributor.authorHansson, Karin
dc.contributor.authorRadke, Katarzyna
dc.contributor.authorMartinez, Sonia 
dc.contributor.authorBlanco Aparicio, Carmen 
dc.contributor.authorGarcia-Ruiz, Cristian
dc.contributor.authorWelinder, Charlotte
dc.contributor.authorEsfandyari, Javanshir
dc.contributor.authorO'Neill, Michael
dc.contributor.authorPastor Fernandez, Joaquin 
dc.contributor.authorvon Stedingk, Kristoffer
dc.contributor.authorBexell, Daniel
dc.identifier.citationEMBO Mol Med. 2019 ;11(8):e10058es_ES
dc.description.abstractThe PI3K pathway is a major driver of cancer progression. However, clinical resistance to PI3K inhibition is common. IBL-302 is a novel highly specific triple PIM, PI3K, and mTOR inhibitor. Screening IBL-302 in over 700 cell lines representing 47 tumor types identified neuroblastoma as a strong candidate for PIM/PI3K/mTOR inhibition. IBL-302 was more effective than single PI3K inhibition in vitro, and IBL-302 treatment of neuroblastoma patient-derived xenograft (PDX) cells induced apoptosis, differentiated tumor cells, and decreased N-Myc protein levels. IBL-302 further enhanced the effect of the common cytotoxic chemotherapies cisplatin, doxorubicin, and etoposide. Global genome, proteome, and phospho-proteome analyses identified crucial biological processes, including cell motility and apoptosis, targeted by IBL-302 treatment. While IBL-302 treatment alone reduced tumor growth in vivo, combination therapy with low-dose cisplatin inhibited neuroblastoma PDX growth. Complementing conventional chemotherapy treatment with PIM/PI3K/mTOR inhibition has the potential to improve clinical outcomes and reduce severe late effects in children with high-risk neuroblastoma.es_ES
dc.description.sponsorshipThis work was supported by funding from the Swedish Cancer Society (to SM, DB), the Swedish Research Council (to DB), the Swedish Childhood Cancer Fund (to SM, KvS, DB), Region Skåne and the research funds of Skåne University Hospital (to DB), the Mary Bevé Foundation (to SM, KvS, DB), Magnus Bergvalls stiftelse (to SM, DB), the Thelma Zoéga Foundation (to SM), Hans von Kantzow Foundation (to SM), Crafoord Foundation (to DB), Åke Wiberg Foundation (to DB), Jeanssons Stiftelser (to DB), Ollie och Elof Ericssons stiftelser (to DB), Berth von Kantzows stiftelse (to DB), the Royal Physiographic Society of Lund (to SM, DB), and the Spanish Ministry of Health and Social Policy (ADE 08 / 90038 ) and the Spanish Ministry of Science and Innovation (CIT- 090000 - 2008 - 14 ) (to JP, SMa, CBA). We would like to thank the Local MS Support at Medical Faculty, Lund University. The authors would like to acknowledge support of the National Genomics Infrastructure (NGI)/Uppsala Genome Center and UPPMAX for providing assistance in massive parallel sequencing and computational infrastructure. Work performed at NGI/Uppsala Genome Center has been funded by RFI/VR and Science for Life Laboratory, Swedenes_ES
dc.publisherWiley es_ES
dc.subjectmultikinase inhibitiones_ES
dc.titleAnti-tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL-302 in neuroblastomaes_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.contributor.funderSwedish Research Council
dc.contributor.funderSwedish Cancer Society
dc.contributor.funderRegion Skane
dc.contributor.funderMagnus Bergvalls stiftelse
dc.contributor.funderSkane University Hospital
dc.contributor.funderMary Beve Foundation
dc.contributor.funderThelma Zoega Foundation
dc.contributor.funderHans von Kantzow Foundation
dc.contributor.funderCrafoord Foundation
dc.contributor.funderOllie och Elof Ericssons stiftelser
dc.contributor.funderAke Wiberg Foundation
dc.contributor.funderBerth von Kantzows stiftelse
dc.contributor.funderRoyal Physiographic Society of Lund
dc.contributor.funderMinisterio de Ciencia e Innovación (España)
dc.contributor.funderJeanssons Stiftelser
dc.contributor.funderScience for Life Laboratory, Sweden
dc.identifier.journalEMBO molecular medicinees_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Sección de Química Médicaes_ES
dc.rights.accessRightsopen accesses_ES

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Atribución-NoComercial-CompartirIgual 4.0 Internacional
This item is licensed under a: Atribución-NoComercial-CompartirIgual 4.0 Internacional