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dc.contributor.author Madorsky Rowdo, Florencia Paula
dc.contributor.author Baron, Antonela
dc.contributor.author Von Euw, Erika María
dc.contributor.author Mordoh, Jose
dc.date.available 2018-10-25T19:30:47Z
dc.date.issued 2017-03
dc.identifier.citation Madorsky Rowdo, Florencia Paula; Baron, Antonela; Von Euw, Erika María; Mordoh, Jose; In vitro long-term treatment with MAPK inhibitors induces melanoma cells with resistance plasticity to inhibitors while retaining sensitivity to CD8 T cells; Spandidos Publications; Oncology Reports; 37; 3; 3-2017; 1367-1378
dc.identifier.issn 1021-335X
dc.identifier.uri http://hdl.handle.net/11336/63094
dc.description.abstract The development of BRAF V600 and MEK inhibitors constitutes a breakthrough in the treatment of patients with BRAF-mutated metastatic melanoma. However, although there is an increase in overall survival, these patients generally confront recurrence, and several resistance mechanisms have already been described. In the present study we describe a different resistance mechanism. After several weeks of long-term in vitro treatment of two different V600E BRAF-mutated melanoma cell lines with MARK inhibitors, PLX4032 and/or GDC-0973, the majority of the cells died whereas some remained viable and quiescent (SUR). Markedly, discontinuing treatment of SUR cells with MAPK inhibitors allowed the population to regrow and these cells retained drug sensitivity equal to that of the parental cells. SUR cells had increased expression levels of CD271 and ABCB5 and presented senescence-associated characteristics. Notably, SUR cells were efficiently lysed by cytotoxic T lymphocytes recognizing MART-1 and gp100 melanoma differentiation antigens. We propose quiescent plasticity as a mechanism of resistance to BRAF and MEK inhibitors while retaining sensitivity to immune effectors.
dc.format application/pdf
dc.language.iso eng
dc.publisher Spandidos Publications
dc.rights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject BRAF
dc.subject GDC-0973
dc.subject MELANOMA
dc.subject PHENOTYPIC PLASTICITY
dc.subject PLX4032
dc.subject.classification Inmunología
dc.subject.classification Medicina Básica
dc.subject.classification CIENCIAS MÉDICAS Y DE LA SALUD
dc.title In vitro long-term treatment with MAPK inhibitors induces melanoma cells with resistance plasticity to inhibitors while retaining sensitivity to CD8 T cells
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2018-10-25T13:35:28Z
dc.journal.volume 37
dc.journal.number 3
dc.journal.pagination 1367-1378
dc.journal.pais Grecia
dc.journal.ciudad Atenas
dc.description.fil Fil: Madorsky Rowdo, Florencia Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
dc.description.fil Fil: Baron, Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
dc.description.fil Fil: Von Euw, Erika María. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of California at Los Angeles; Estados Unidos
dc.description.fil Fil: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
dc.journal.title Oncology Reports
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3892/or.2017.5363
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/https://www.spandidos-publications.com/10.3892/or.2017.5363
dc.conicet.fuente Elsevier


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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)