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<p>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.</p>

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Dissecting endometrial cancer complexity in response to standard and targeted therapies

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月28日

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  • Sebastiano Vaccarella,
  • Valentina Bruno,
  • Giulia Orlandi,
  • Daniela Angela Covino,
  • Carlotta Frascolla,
  • Claudio Pulito,
  • Riccardo Vizza,
  • Giulia Urbani,
  • Matteo Allegretti,
  • Valentina De Pascale,
  • Frauke Goeman,
  • Ludovica Ciuffreda,
  • Brindusa Ana Maria Arteni,
  • Simona Di Martino,
  • Andrea Sacconi,
  • Emanuela Mancini,
  • Anna Bagnato,
  • Ermelinda Baiocco,
  • Ramy Kajal,
  • Yaron Vinik,
  • Sima Lev,
  • Maurizio Fanciulli,
  • Antonello Vidiri,
  • Mariantonia Carosi,
  • Sabrina Strano,
  • Sara Donzelli,
  • Enrico Vizza,
  • Giovanni Blandino

摘要

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.