Related Experiment Video
Updated: Aug 22, 2025
High-Throughput In Vitro Assay using Patient-Derived Tumor Organoids
Published on: June 14, 2021
Generation and Integrated Analysis of Advanced Patient-Derived Orthoxenograft Models (PDOX) for the Rational
Laura Devis-Jauregui1, August Vidal2, Laura Plata-Peña1
1Molecular Mechanisms and Experimental Therapy in Oncology-Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, 08908, Spain.
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.
Insights
This study introduces patient-derived orthoxenograft (PDOX) mouse models for endometrial cancer (EC), offering a new platform for precision medicine. These models accurately reflect patient tumors, enabling the testing of targeted therapies like trastuzumab.
Area of Science:
- Oncology
- Translational Research
- Genomics
Background:
- Endometrial cancer (EC) treatment is limited by a lack of effective second-line therapies and predictive biomarkers.
- Patient survival rates for EC have stagnated over the past four decades.
- Existing experimental systems hinder translational studies and clinical advancements in EC.
Purpose of the Study:
- To generate and characterize endometrioid-EC patient-derived orthoxenograft (PDOX) mouse models.
- To establish a reliable experimental system for precision medicine in EC.
- To evaluate the therapeutic potential of trastuzumab in EC using these novel models.
Main Methods:
- Generation of a collection of EC patient-derived orthoxenograft (PDOX) mouse models.
- Integrative characterization using transcriptomics, mutational profiling, and morphological analysis.
- Assessment of trastuzumab efficacy using patient-derived organotypic multicellular tumor spheroids and in vivo PDOX models.
Main Results:
- EC PDOX models successfully retained key molecular and morphological features of the original patient tumors.
- The study demonstrated the utility of PDOX models for evaluating targeted therapies.
- Trastuzumab's therapeutic potential was assessed in both spheroid and in vivo models.
Conclusions:
- The developed EC PDOX models represent a significant advancement for preclinical research and translational studies.
- These models overcome experimental limitations, paving the way for precision medicine in EC.
- The findings support further investigation of HER2-targeted therapies, such as trastuzumab, in EC treatment.
