Preclinical study of microphthalmia-associated transcription factor inhibitor ML329 in gastrointestinal stromal tumor growth

Gastrointestinal stromal tumors (GISTs) comprise about 80% of mesenchymal neoplasms in the gastrointestinal tract. Although imatinib mesylate is the preferred treatment, the development of drug resistance highlights the need for novel therapeutic strategies. Recently, we have identified the micropht...

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Autores: Guerrero, Mario, Proaño Pérez, Elizabeth, Serrano Candelas, Eva, 1982-, García Valverde, Alfonso, Carrillo Rodríguez, Berenice, Rosell, Jordi, Serrano, César, Martín Andorrà, Margarita
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/223830
Acesso em linha:https://hdl.handle.net/2445/223830
Access Level:acceso abierto
Palavra-chave:Càncer gastrointestinal
Cicle cel·lular
Tumors
Factors de transcripció
Gastrointestinal cancer
Cell cycle
Transcription factors
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spelling Preclinical study of microphthalmia-associated transcription factor inhibitor ML329 in gastrointestinal stromal tumor growthGuerrero, MarioProaño Pérez, ElizabethSerrano Candelas, Eva, 1982-García Valverde, AlfonsoCarrillo Rodríguez, BereniceRosell, JordiSerrano, CésarMartín Andorrà, MargaritaCàncer gastrointestinalCicle cel·lularTumorsFactors de transcripcióGastrointestinal cancerCell cycleTumorsTranscription factorsGastrointestinal stromal tumors (GISTs) comprise about 80% of mesenchymal neoplasms in the gastrointestinal tract. Although imatinib mesylate is the preferred treatment, the development of drug resistance highlights the need for novel therapeutic strategies. Recently, we have identified the microphthalmia-associated transcription factor (MITF) as a critical player in pro-survival signaling and tumor growth. This study investigates the effects of MITF inhibition using ML329, an MITF pathway inhibitor, on GIST cell viability in vitro and in NMRI-nu/nu mouse xenograft models. ML329 suppresses growth in imatinib-sensitive (GIST-T1) and -resistant (GIST 430/654) cell lines, impairs MITF targets such as BCL2 and CDK2, and induces S-G2/M cell-cycle arrest. In vivo, ML329 is well tolerated and significantly reduces tumor growth in established imatinib-sensitive and -resistant GIST models. These findings underscore the importance of MITF in GIST growth and support its inhibition as a promising therapeutic approach.Elsevier2025202520252025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion8 p.application/pdfhttps://hdl.handle.net/2445/223830Articles publicats en revistes (Biomedicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1016/j.omton.2025.200983Molecular Therapy Oncolytics, 2025, vol. 33, num.2https://doi.org/10.1016/j.omton.2025.200983cc-by (c) Guerrero, Mario et al., 2025http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2238302026-05-29T05:05:01Z
dc.title.none.fl_str_mv Preclinical study of microphthalmia-associated transcription factor inhibitor ML329 in gastrointestinal stromal tumor growth
title Preclinical study of microphthalmia-associated transcription factor inhibitor ML329 in gastrointestinal stromal tumor growth
spellingShingle Preclinical study of microphthalmia-associated transcription factor inhibitor ML329 in gastrointestinal stromal tumor growth
Guerrero, Mario
Càncer gastrointestinal
Cicle cel·lular
Tumors
Factors de transcripció
Gastrointestinal cancer
Cell cycle
Tumors
Transcription factors
title_short Preclinical study of microphthalmia-associated transcription factor inhibitor ML329 in gastrointestinal stromal tumor growth
title_full Preclinical study of microphthalmia-associated transcription factor inhibitor ML329 in gastrointestinal stromal tumor growth
title_fullStr Preclinical study of microphthalmia-associated transcription factor inhibitor ML329 in gastrointestinal stromal tumor growth
title_full_unstemmed Preclinical study of microphthalmia-associated transcription factor inhibitor ML329 in gastrointestinal stromal tumor growth
title_sort Preclinical study of microphthalmia-associated transcription factor inhibitor ML329 in gastrointestinal stromal tumor growth
dc.creator.none.fl_str_mv Guerrero, Mario
Proaño Pérez, Elizabeth
Serrano Candelas, Eva, 1982-
García Valverde, Alfonso
Carrillo Rodríguez, Berenice
Rosell, Jordi
Serrano, César
Martín Andorrà, Margarita
author Guerrero, Mario
author_facet Guerrero, Mario
Proaño Pérez, Elizabeth
Serrano Candelas, Eva, 1982-
García Valverde, Alfonso
Carrillo Rodríguez, Berenice
Rosell, Jordi
Serrano, César
Martín Andorrà, Margarita
author_role author
author2 Proaño Pérez, Elizabeth
Serrano Candelas, Eva, 1982-
García Valverde, Alfonso
Carrillo Rodríguez, Berenice
Rosell, Jordi
Serrano, César
Martín Andorrà, Margarita
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer gastrointestinal
Cicle cel·lular
Tumors
Factors de transcripció
Gastrointestinal cancer
Cell cycle
Tumors
Transcription factors
topic Càncer gastrointestinal
Cicle cel·lular
Tumors
Factors de transcripció
Gastrointestinal cancer
Cell cycle
Tumors
Transcription factors
description Gastrointestinal stromal tumors (GISTs) comprise about 80% of mesenchymal neoplasms in the gastrointestinal tract. Although imatinib mesylate is the preferred treatment, the development of drug resistance highlights the need for novel therapeutic strategies. Recently, we have identified the microphthalmia-associated transcription factor (MITF) as a critical player in pro-survival signaling and tumor growth. This study investigates the effects of MITF inhibition using ML329, an MITF pathway inhibitor, on GIST cell viability in vitro and in NMRI-nu/nu mouse xenograft models. ML329 suppresses growth in imatinib-sensitive (GIST-T1) and -resistant (GIST 430/654) cell lines, impairs MITF targets such as BCL2 and CDK2, and induces S-G2/M cell-cycle arrest. In vivo, ML329 is well tolerated and significantly reduces tumor growth in established imatinib-sensitive and -resistant GIST models. These findings underscore the importance of MITF in GIST growth and support its inhibition as a promising therapeutic approach.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/223830
url https://hdl.handle.net/2445/223830
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.omton.2025.200983
Molecular Therapy Oncolytics, 2025, vol. 33, num.2
https://doi.org/10.1016/j.omton.2025.200983
dc.rights.none.fl_str_mv cc-by (c) Guerrero, Mario et al., 2025
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Guerrero, Mario et al., 2025
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 8 p.
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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