Modeling anti-IL-6 therapy using breast cancer patient-derived xenografts
Morancho, Beatriz (Hospital Universitari Vall d'Hebron)
Zacarías-Fluck, Mariano F (Hospital Universitari Vall d'Hebron)
Esgueva, Antonio (Hospital Universitari Vall d'Hebron)
Bernadó Morales, Cristina (Hospital Universitari Vall d'Hebron)
Cosimo, Serena Di (Division of Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy)
Prat, Aleix (Hospital Universitari Vall d'Hebron)
Cortés, Javier (Hospital Universitari Vall d'Hebron)
Arribas, Joaquín V (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Rubio, Isabel T. (Hospital Universitari Vall d'Hebron)

Date:	2016
Abstract:	The pleiotropic cytokine IL-6 accelerates the progression of breast cancer in a variety of preclinical models through the activation of the STAT3 (signal transducer and activator of transcription 3) signaling pathway. However, the proportion of breast cancers sensitive to anti-IL-6 therapies is not known. This study evaluates the efficacy of anti-IL-6 therapies using breast cancer patient derived xenografts (PDXs). During the generation of our collection of PDXs, we showed that the successful engraftment of tumor tissue in immunodeficient mice correlates with bad prognosis. Four PDXs out of six were resistant to anti-IL-6 therapies and the expression of IL-6, its receptor or the levels of phospho-STAT3 (the active form of the signal transducer) did not correlate with sensitivity. Using cell cultures established from the PDXs as well as samples from in vivo treatments, we showed that only tumors in which the activation of STAT3 depends on IL-6 respond to the blocking antibodies. Our results indicate that only a fraction of breast tumors are responsive to anti-IL-6 therapies. In order to identify responsive tumors, a functional assay to determine the dependence of STAT3 activation on IL-6 should be performed.
Grants:	Instituto de Salud Carlos III PI11-02496 Instituto de Salud Carlos III RD12-0036-0057 Instituto de Salud Carlos III PI12-02536 Instituto de Salud Carlos III RTICC-RD12-0036
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Breast cancer ; IL-6 ; STAT3 ; Patient-derived xenografts
Published in:	Oncotarget, Vol. 7 (september 2016) , p. 67956-67965, ISSN 1949-2553

DOI: 10.18632/oncotarget.11815
PMID: 27602583

10 p, 3.3 MB

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