Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients

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 - Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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.

U2 - 10.1126/scitranslmed.aay2574

DO - 10.1126/scitranslmed.aay2574

M3 - Article

C2 - 31597751

SN - 1946-6234

VL - 11

JO - Science Translational Medicine

JF - Science Translational Medicine

IS - 513

ER -