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Title: Generation and integrated analysis of advanced patient-derived orthoxenograft models (PDOX) for the rational assessment of targeted therapies in endometrial cancer
Author: Devis Jauregui, Laura
Vidal-Bel, August
Plata Peña, Laura
Santacana, Maria
García Mulero, Sandra
Bonifaci Cano, Núria
Noguera-Delgado, Eulàlia
Ruiz, Nuria
Gil, Marta
Dorca Duch, Eduard
Llobet, Francisco J.
Coll-Iglesias, Laura
Gassner, Katja
Martínez Iniesta, María
Rodriguez Barrueco, Ruth
Barahona, Marc
Martí, Lola
Viñals Canals, Francesc
Ponce i Sebastià, Jordi
Sanz Pamplona, Rebeca
Piulats, Josep M.
Vivancos, Ana
Matias-Guiu, Xavier
Villanueva Garatachea, Alberto
Llobet Navas, David
Keywords: Càncer d'endometri
Experimentació animal
Endometrial cancer
Animal experimentation
Issue Date: 14-Nov-2022
Publisher: Wiley-VCH Verlag
Abstract: Clinical management of endometrial cancer (EC) is handicapped by the limited availability of second line treatments and bona fide molecular biomarkers to predict recurrence. These limitations have hampered the treatment of these patients, whose survival rates have not improved over the last four decades. The advent of coordinated studies such as The Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma (TCGA_UCEC) has partially solved this issue, but the lack of proper experimental systems still represents a bottleneck that precludes translational studies from successful clinical testing in EC patients. Within this context, the first study reporting the generation of a collection of endometrioid-EC-patient-derived orthoxenograft (PDOX) mouse models is presented that is believed to overcome these experimental constraints and pave the way toward state-of-the-art precision medicine in EC. The collection of primary tumors and derived PDOXs is characterized through an integrative approach based on transcriptomics, mutational profiles, and morphological analysis; and it is demonstrated that EC tumors engrafted in the mouse uterus retain the main molecular and morphological features from analogous tumor donors. Finally, the molecular properties of these tumors are harnessed to assess the therapeutic potential of trastuzumab, a human epidermal growth factor receptor 2 (HER2) inhibitor with growing interest in EC, using patient-derived organotypic multicellular tumor spheroids and in vivo experiments.
Note: Reproducció del document publicat a:
It is part of: Advanced Science, 2022, vol. 10, num. 1, p. e2204211
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ISSN: 2198-3844
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Fisiològiques)

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