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journal article·2023-01Open access

Generation and Integrated Analysis of Advanced Patient‐Derived Orthoxenograft Models (PDOX) for the Rational Assessment of Targeted Therapies in Endometrial Cancer

Laura Devis‐Jauregui, August Vidal, Laura Plata‐Peña, Maria Santacana, Sandra García‐Mulero, Nuria Bonifaci, Eulàlia Noguera‐Delgado, Nuria Ruiz, Marta Gil, Eduard Dorca, Francisco J. Llobet, Laura Coll‐Iglesias, Katja Gassner, Maria Martinez‐Iniesta, Ruth Rodriguez‐Barrueco, Marc Barahona, Lola Marti, Francesc Viñals, Jordi Ponce, Rebeca Sanz‐Pamplona, Josep M. Piulats, Ana Vivancos, Xavier Matias‐Guiu, Alberto Villanueva, David Llobet‐Navas

Advanced Science· Volume 10· Issue 1
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Source abstract

Abstract

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.
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Research context

OpenAlex topics: Endometrial and Cervical Cancer Treatments · Angiogenesis and VEGF in Cancer · RNA Research and Splicing

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Molecular Mechanisms and Experimental Therapy in Oncology‐Oncobell Program Bellvitge Biomedical Research Institute (IDIBELL) L'Hospitalet de Llobregat Barcelona 08908 Spain

Department of Pathology University Hospital of Bellvitge Bellvitge Biomedical Research Institute (IDIBELL) L'Hospitalet de Llobregat Barcelona 08908 Spain

Scientific and Technical Service of Immunohistochemistry Lleida Institute for Biomedical Research Dr. Pifarré Foundation IRBLleida Hospital Universitari Arnau de Vilanova Lleida 25198 Spain

Department of Pathology Universitat de Lleida/Institut de Recerca Biomèdica de Lleida/Hospital Universitari Arnau de Vilanova Lleida 25198 Spain

Unit of Biomarkers and Susceptibility Oncology Data Analytics Program (ODAP) Catalan Institute of Oncology (ICO) Oncobell Program Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP L'Hospitalet de Llobregat Barcelona 08908 Spain

Department of Basic Sciences Universitat de Lleida/Institut de Recerca Biomèdica de Lleida Edifici Biomedicina I, Lab 2.4 Lleida 25198 Spain

Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) Instituto de Salud Carlos III (ISCIII) Madrid 28029 Spain

Catalan Institute of Oncology (ICO) Bellvitge Biomedical Research Institute (IDIBELL) L'Hospitalet de Llobregat Barcelona Barcelona 08908 Spain

Chemoresistance and Predictive Factors Group Program Against Cancer Therapeutic Resistance (ProCURE) Catalan Institute of Oncology (ICO) Bellvitge Biomedical Research Institute (IDIBELL) L'Hospitalet de Llobregat Barcelona 08908 Spain

Anatomy Unit Department of Pathology and Experimental Therapy School of Medicine University of Barcelona (UB) L'Hospitalet de Llobregat Barcelona 08907 Spain

Department of Gynaecology University Hospital of Bellvitge Bellvitge Biomedical Research Institute (IDIBELL) L'Hospitalet de Llobregat Barcelona 08908 Spain

Department of Physiological Sciences School of Medicine University of Barcelona (UB) L'Hospitalet de Llobregat Barcelona 08907 Spain

Cancer Genomics Group Vall d'Hebron Institute of Oncology (VHIO) Barcelona 08035 Spain

Xenopat S.L. Parc Cientific de Barcelona (PCB) Barcelona 08028 Spain

Funding

JGW Patterson Foundation

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