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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
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Phenotypic Plasticity
dc.subject
Plx4032
dc.subject.classification
Inmunología
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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


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