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Patient-derived organoids model treatment response of metastatic gastrointestinal cancers

Autori:

  • GEORGIOS VLACHOGIANNIS, SOMAIEH HEDAYAT, ALEXANDRA VATSIOU, YANN JAMIN, JAVIER FERNÁNDEZ-MATEOS, KHURUM KHAN, ANDREA LAMPIS, KATHERINE EASON, IAN HUNTINGFORD, ROSEMARY BURKE, MIHAELA RATA, DOW-MU KOH, NINA TUNARIU, DAVID COLLINS, SANNA HULKKI-WILSON, CHANTHIRIKA RAGULAN, INMACULADA SPITERI, SING YU MOORCRAFT, IAN CHAU, SHEELA RAO, DAVID WATKINS. NICOS FOTIADIS, MARIA BALI, MAHNAZ DARVISH-DAMAVANDI, HAZEL LOTE, ZAKARIA ELTAHIR, ELIZABETH C. SMYTH, RUWAIDA BEGUM, PAUL A. CLARKE, JENS C. HAHNE, MITCHELL DOWSETT, JOHANN DE BONO, PAUL WORKMAN, ANGURAJ SADANANDAM, MATTEO FASSAN, OWEN J. SANSOM, SUZANNE ECCLES, NAUREEN STARLING, CHIARA BRACONI,,
  • Sottoriva A.,
  •  SIMON P. ROBINSON, DAVID CUNNINGHAM, AND NICOLA VALERI

Sommario:

Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from metastatic, heavily pretreated colorectal and gastroesophageal cancer patients recruited in phase 1/2 clinical trials. Phenotypic and genotypic profiling of PDOs showed a high degree of similarity to the original patient tumors. Molecular profiling of tumor organoids was matched to drug-screening results, suggesting that PDOs could complement existing approaches in defining cancer vulnerabilities and improving treatment responses. We compared responses to anticancer agents ex vivo in organoids and PDO-based orthotopic mouse tumor xenograft models with the responses of the patients in clinical trials. Our data suggest that PDOs can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs.

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