Dissecting endometrial cancer complexity in response to standard and targeted therapies
Endometrial cancer (EC) is one of the most common gynecologic malignancies amongst women worldwide. Its incidence and mortality rates have been increasing in the last decade. In the present work, we built a patient EC-derived organoid (PDOs) platform that faithfully recapitulated tumor phenotype, genomic alterations, and expression profiles of matched-primary cancer tissues. Interestingly, we found that the response of EC-derived PDOs to both standard therapy and a wide range of targeted drugs accordingly to their specific druggable genetic alterations was congruent with that of the originating patients. We also isolated and genomically characterized matched-PDO stromal cells, specifically cancer-associated fibroblasts (CAFs). Unlike PDOs matched CAFs were poorly responsive and underwent to pro-inflammatory senescence upon treatment with standard therapy. Collectively, our findings established a EC-PDOs preclinical platform which allows assessing the therapeutic response of tumor and surrounding tumor microenvironment cellular landscape.
Authors
- Yaron Vinik (ORCID: https://orcid.org/0000-0003-3344-5922)
- Sabrina Strano (ORCID: https://orcid.org/0000-0002-6341-4230)
- Antonello Vidiri
- Ludovica Ciuffreda (ORCID: https://orcid.org/0000-0002-7964-7119)
- Matteo Allegretti (ORCID: https://orcid.org/0000-0003-3398-8775)
- Daniela Angela Covino (ORCID: https://orcid.org/0000-0003-2606-5534)
- Carlotta Frascolla
- Enrico Vizza (ORCID: https://orcid.org/0000-0001-5915-4555)
- Simona Di Martino (ORCID: https://orcid.org/0000-0003-4533-3776)
- Valentina Bruno (ORCID: https://orcid.org/0000-0002-0008-9573)
- Valentina De Pascale (ORCID: https://orcid.org/0000-0003-1015-8867)
- Mariantonia Carosi (ORCID: https://orcid.org/0000-0002-6298-7168)
- Frauke Goeman (ORCID: https://orcid.org/0000-0002-7803-8821)
- Sara Donzelli (ORCID: https://orcid.org/0000-0002-8529-2895)
- Ermelinda Baiocco (ORCID: https://orcid.org/0000-0002-5719-5561)
- Riccardo Vizza (ORCID: https://orcid.org/0009-0000-7401-8965)
- Giovanni Blandino (ORCID: https://orcid.org/0000-0002-6970-2241)
- Sima Lev (ORCID: https://orcid.org/0000-0002-2108-3330)
- Giulia Orlandi (ORCID: https://orcid.org/0000-0003-2627-1979)
- Maurizio Fanciulli (ORCID: https://orcid.org/0000-0002-5281-4191)
- Emanuela Mancini (ORCID: https://orcid.org/0000-0002-9946-7289)
- Andrea Sacconi (ORCID: https://orcid.org/0000-0002-8276-0438)
- Claudio Pulito (ORCID: https://orcid.org/0000-0002-0921-6962)
- G Urbani (ORCID: https://orcid.org/0009-0009-1343-3415)
- Anna Bagnato (ORCID: https://orcid.org/0000-0002-7269-9522)
- Sebastiano Vaccarella (ORCID: https://orcid.org/0009-0005-1937-4699)
- Brindusa Ana Maria Arteni
- Ramy Kajal
Institutions
- National Cancer Institute (MY)
- Istituti Fisioterapici Ospitalieri (IT)
- San Gallicano Hospital (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Weizmann Institute of Science (IL)
Publication Details
- Journal
- Cell Death and Disease
- Published
- 2025-11-28
- DOI
- https://doi.org/10.1038/s41419-025-08051-8
- Citations
- 2
- Primary Topic
- Cancer Cells and Metastasis
- Type
- article
- Field-Weighted Citation Impact
- 2.09