Multicenter study correlating molecular characteristics and clinical outcomes of cancer cases with patient-derived organoids

多中心研究将癌症病例的分子特征和临床结果与患者来源的类器官联系起来

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作者:Paloma Navarro # ,Tatiana P Grazioso # ,Arantzazu Barquín ,Maria Barba ,Mónica Yagüe ,Carlos Millán ,Irene López ,Elena Sevillano ,Miguel Quiralte ,Paloma Fernández ,Diego Losada ,Eduardo Caleiras ,Julia Calzas ,Beatriz Jiménez ,Sergio Ruiz-Llorente ,Juan Justo ,Félix Guerrero ,Vital Hevia ,Raquel Martín ,Francisco José Pérez-Rodriguez ,Julia Tejerina ,Mario Prieto ,Paula Comune ,Juan Francisco Rodriguez-Moreno ,Jesús García-Donás

Abstract

Background: 3D-spatial interaction between cancer cells influences tumor behavior, making it essential to replicate tumor structures for predicting patient outcomes. Methods: We collected data from three multicenter prospective studies to evaluate the ability to establish Patient-Derived Organoids (PDOs) from different biological samples and timepoints, correlating their characteristics and drug sensitivity with clinical outcomes. Results: From 184 patients (17 tumor types), 249 samples were collected: 149 (59.8%) from tumor tissue, 61 (24.5%) from peritoneal fluids, 39 (15.7%) from peripheral blood. Success rates for PDO establishment were 39.5%, 34.4%, and 25.6%, respectively. PDOs reproduced pathological and immunohistochemical patterns of source tumors, with pathogenic variants confirmed in 84% (21/25). In a series of 13 baseline and sequential PDOs from 9 patients undergoing treatment, responses to therapy mirrored patient responses during therapy. Conclusions: PDOs preserve tumor features, reflect disease progression, and predict treatment responses, providing valuable models to complement molecular testing in precision medicine.

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