 visitante ::
identificación
|
|||||||||||||||
|
Buscar | Enviar | Ayuda | Servicio de Bibliotecas | Sobre el DDD | Català English Español | |||||||||
| Página principal > Artículos > Artículos publicados > Expanding a precision medicine platform for malignant peripheral nerve sheath tumors : |
(Institut Germans Trias i Pujol) (Hospital Universitari Vall d'Hebron) (Institut Català d'Oncologia) (Institut Català d'Oncologia) (Institut Germans Trias i Pujol) (Institut Germans Trias i Pujol) (Institut Germans Trias i Pujol) (Institut Germans Trias i Pujol) (Centro de Investigación Biomédica en Red de Cáncer)
| Fecha: | 2024 |
| Resumen: | Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft-tissue sarcomas with a poor survival rate, presenting either sporadically or in the context of neurofibromatosis type 1 (NF1). The histological diagnosis of MPNSTs can be challenging, with different tumors exhibiting great histological and marker expression overlap. This heterogeneity could be partly responsible for the observed disparity in treatment response due to the inherent diversity of the preclinical models used. For several years, our group has been generating a large patient-derived orthotopic xenograft (PDOX) MPNST platform for identifying new precision medicine treatments. Herein, we describe the expansion of this platform using six primary tumors clinically diagnosed as MPNSTs, from which we obtained six additional PDOX mouse models and three cell lines, thus generating three pairs of in vitro-in vivo models. We extensively characterized these tumors and derived preclinical models, including genomic, epigenomic, and histological analyses. Tumors were reclassified after these analyses: three remained as MPNSTs (two being classic MPNSTs), one was a melanoma, another was a neurotrophic tyrosine receptor kinase (NTRK)-rearranged spindle cell neoplasm, and, finally, the last was an unclassifiable tumor bearing neurofibromin-2 (NF2) inactivation, a neuroblastoma RAS viral oncogene homolog (NRAS) oncogenic mutation, and a SWI/SNF-related matrix-associated actin-dependent regulator of chromatin (SMARCA4) heterozygous truncated variant. New cell lines and PDOXs faithfully recapitulated histology, marker expression, and genomic characteristics of the primary tumors. The diversity in tumor identity and their specific associated genomic alterations impacted treatment responses obtained when we used the new cell lines for testing compounds against known altered pathways in MPNSTs. In summary, we present here an extension of our MPNST precision medicine platform, with new PDOXs and cell lines, including tumor entities confounded as MPNSTs in a real clinical scenario. This platform may constitute a useful tool for obtaining correct preclinical information to guide MPNST clinical trials. |
| Ayudas: | Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-01112 Instituto de Salud Carlos III PI19/00553 Ministerio de Economía y Competitividad PI16/00563 Ministerio de Economía y Competitividad PI16/01898 Instituto de Salud Carlos III PI20/00228 |
| Derechos: | 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.  |
| Lengua: | Anglès |
| Documento: | Article ; recerca ; Versió publicada |
| Publicado en: | Molecular oncology, Vol. 18 Núm. 4 (april 2024) , p. 895-917, ISSN 1878-0261 |
