TY - JOUR
T1 - Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients
AU - Ooft, Salo N.
AU - Weeber, Fleur
AU - Dijkstra, Krijn K.
AU - McLean, Chelsea M.
AU - Kaing, Sovann
AU - van Werkhoven, Erik
AU - Schipper, Luuk
AU - Hoes, Louisa
AU - Vis, Daniel J.
AU - van de Haar, Joris
AU - Prevoo, Warner
AU - Snaebjornsson, Petur
AU - van der Velden, Daphne
AU - Klein, Michelle
AU - Chalabi, Myriam
AU - Boot, Henk
AU - van Leerdam, Monique
AU - Bloemendal, Haiko J.
AU - Beerepoot, Laurens V.
AU - Wessels, Lodewyk
AU - Cuppen, Edwin
AU - Clevers, Hans
AU - Voest, Emile E.
N1 - Publisher Copyright:
Copyright © 2019 The Authors,
PY - 2019/10/9
Y1 - 2019/10/9
N2 - There is a clear and unmet clinical need for biomarkers to predict responsiveness to chemotherapy for cancer. We developed an in vitro test based on patient-derived tumor organoids (PDOs) from metastatic lesions to identify nonresponders to standard-of-care chemotherapy in colorectal cancer (CRC). In a prospective clinical study, we show the feasibility of generating and testing PDOs for evaluation of sensitivity to chemotherapy. Our PDO test predicted response of the biopsied lesion in more than 80% of patients treated with irinotecan-based therapies without misclassifying patients who would have benefited from treatment. This correlation was specific to irinotecan-based chemotherapy, however, and the PDOs failed to predict outcome for treatment with 5-fluorouracil plus oxaliplatin. Our data suggest that PDOs could be used to prevent cancer patients from undergoing ineffective irinotecan-based chemotherapy.
AB - There is a clear and unmet clinical need for biomarkers to predict responsiveness to chemotherapy for cancer. We developed an in vitro test based on patient-derived tumor organoids (PDOs) from metastatic lesions to identify nonresponders to standard-of-care chemotherapy in colorectal cancer (CRC). In a prospective clinical study, we show the feasibility of generating and testing PDOs for evaluation of sensitivity to chemotherapy. Our PDO test predicted response of the biopsied lesion in more than 80% of patients treated with irinotecan-based therapies without misclassifying patients who would have benefited from treatment. This correlation was specific to irinotecan-based chemotherapy, however, and the PDOs failed to predict outcome for treatment with 5-fluorouracil plus oxaliplatin. Our data suggest that PDOs could be used to prevent cancer patients from undergoing ineffective irinotecan-based chemotherapy.
UR - http://www.scopus.com/inward/record.url?scp=85073117042&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.aay2574
DO - 10.1126/scitranslmed.aay2574
M3 - Article
C2 - 31597751
AN - SCOPUS:85073117042
SN - 1946-6234
VL - 11
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 513
M1 - eaay2574
ER -