2026-04-17T03:27:12Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/131212025-06-14T04:13:27Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Guerrero, Mario author PROAÑO PEREZ, ELIZABETH author Serrano Candelas, Eva author García-Valverde, Alfonso author Carrillo Rodriguez, Berenice author Rosell, Jordi author Serrano, Cesar author 2025-05-22T08:47:54Z 2025-05-22T08:47:54Z 2025-06-18 Cell cycle; Cell survival; Gastrointestinal stromal tumors Ciclo celular; Supervivencia celular; Tumores del estroma gastrointestinal Cicle cel·lular; Supervivència cel·lular; Tumors de l'estroma gastrointestinal 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. We are indebted to the Cytomics core facility of the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) for technical support. This study has been funded by a grant from the Spanish Ministry of Science, Innovation and Universities (MICIU) and European Regional Development Fund (ERDF)/European Social Fund “Investing in your future”: RTI2018-096915-B100 (M.M.) and PID2021-122898OB-I00 (M.M.) was funded by MICIU/AEI/10.13039/501100011033/ and by ERDF, EU. The study has also been funded by Asociación Española Contra el Cáncer (AECC CLSEN20004SERR) (C.S.) and ISCIII PI22_00720 (C.S.). http://hdl.handle.net/11351/13121 Aparell digestiu - Càncer - Tractament Tub digestiu - Càncer - Tractament Resistència als medicaments Medicaments antineoplàstics - Ús terapèutic CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Basic Helix-Loop-Helix Transcription Factors::Basic Helix-Loop-Helix Leucine Zipper Transcription Factors::Microphthalmia-Associated Transcription Factor Other subheadings::Other subheadings::Other subheadings::/antagonists & inhibitors DISEASES::Digestive System Diseases::Digestive System Neoplasms::Gastrointestinal Neoplasms::Digestive System Diseases::Gastrointestinal Stromal Tumors Other subheadings::Other subheadings::Other subheadings::/drug therapy DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms PHENOMENA AND PROCESSES::Physiological Phenomena::Pharmacological and Toxicological Phenomena::Pharmacological Phenomena::Drug Resistance::Drug Resistance, Neoplasm COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas de unión al ADN::factores de transcripción con hélice-asa-hélice básico::factores de transcripción con hélice-asa-hélice y cremallera de leucina básicos::factor de transcripción asociado a la microftalmía Otros calificadores::Otros calificadores::Otros calificadores::/antagonistas & inhibidores ENFERMEDADES::enfermedades del sistema digestivo::neoplasias del sistema digestivo::neoplasias gastrointestinales::enfermedades del sistema digestivo::tumores del estroma gastrointestinal Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales FENÓMENOS Y PROCESOS::fenómenos fisiológicos::fenómenos farmacológicos y toxicológicos::fenómenos farmacológicos::resistencia a medicamentos::resistencia a los antineoplásicos Preclinical study of microphthalmia-associated transcription factor inhibitor ML329 in gastrointestinal stromal tumor growth