Genomic Validation of Endometrial Cancer Patient-Derived Xenograft Models as a Preclinical Tool
Villafranca-Magdalena, Beatriz (Universitat Autònoma de Barcelona)
Masferrer-Ferragutcasas, Carina (Universitat Autònoma de Barcelona)
López-Gil, Carlos (Universitat Autònoma de Barcelona)
Coll de la Rubia, Eva (Universitat Autònoma de Barcelona)
Rebull, Marta (Universitat Autònoma de Barcelona)
Parra, Genis (Centre de Regulació Genòmica)
García, Ángel (Hospital Universitari Vall d'Hebron)
Reques, Armando (Hospital Universitari Vall d'Hebron)
Cabrera Díaz, Silvia (Vall d'Hebron Institut d'Oncologia)
Colás Ortega, Eva (Universitat Autònoma de Barcelona)
Gil-Moreno, Antonio 1965- (Vall d'Hebron Institut d'Oncologia)
Moiola, Cristian Pablo (Universitat Autònoma de Barcelona)

Fecha:	2022
Resumen:	Endometrial cancer (EC) is the second most frequent gynecological cancer worldwide. Although improvements in EC classification have enabled an accurate establishment of disease prognosis, women with a high-risk or recurrent EC face a dramatic situation due to limited further treatment options. Therefore, new strategies that closely mimic the disease are required to maximize drug development success. Patient-derived xenografts (PDXs) are widely recognized as a physiologically relevant preclinical model. Hence, we propose to molecularly and histologically validate EC PDX models. To reveal the molecular landscape of PDXs generated from 13 EC patients, we performed histological characterization and whole-exome sequencing analysis of tumor samples. We assessed the similarity between PDXs and their corresponding patient's tumor and, additionally, to an extended cohort of EC patients obtained from The Cancer Genome Atlas (TCGA). Finally, we performed functional enrichment analysis to reveal differences in molecular pathway activation in PDX models. We demonstrated that the PDX models had a well-defined and differentiated molecular profile that matched the genomic profile described by the TCGA for each EC subtype. Thus, we validated EC PDX's potential to reliably recapitulate the majority of histologic and molecular EC features. This work highlights the importance of a thorough characterization of preclinical models for the improvement of the success rate of drug-screening assays for personalized medicine.
Ayudas:	Instituto de Salud Carlos III PI17/02071 Instituto de Salud Carlos III PI20/01566 Ministerio de Ciencia, Innovación y Universidades RTC-2017-6261-1 Ministerio de Economía y Competitividad CB16/12/00328 Generalitat de Catalunya 2017SGR1661 Generalitat de Catalunya PERIS-SLT017/20/000183
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
Materia:	Endometrial cancer ; Preclinical model ; PDXs ; Personalized medicine ; Translational research ; Genomics ; Bioinformatics ; Molecular marker ; TCGA
Publicado en:	International journal of molecular sciences, Vol. 23 (june 2022) , ISSN 1422-0067

DOI: 10.3390/ijms23116266
PMID: 35682944

22 p, 3.0 MB

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