Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients
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). I...
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| Published in | Science translational medicine Vol. 11; no. 513 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
09.10.2019
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| Online Access | Get more information |
| ISSN | 1946-6242 |
| DOI | 10.1126/scitranslmed.aay2574 |
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| Abstract | 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. |
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| AbstractList | 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. |
| Author | Kaing, Sovann van der Velden, Daphne Voest, Emile E Dijkstra, Krijn K Clevers, Hans McLean, Chelsea M Weeber, Fleur Klein, Michelle Ooft, Salo N Bloemendal, Haiko J Chalabi, Myriam Schipper, Luuk van Werkhoven, Erik Snaebjornsson, Petur Boot, Henk Beerepoot, Laurens V van Leerdam, Monique Prevoo, Warner van de Haar, Joris Cuppen, Edwin Hoes, Louisa Vis, Daniel J Wessels, Lodewyk |
| Author_xml | – sequence: 1 givenname: Salo N orcidid: 0000-0002-3990-3376 surname: Ooft fullname: Ooft, Salo N organization: Oncode Institute, 3521 AL Utrecht, Netherlands – sequence: 2 givenname: Fleur orcidid: 0000-0002-8375-9754 surname: Weeber fullname: Weeber, Fleur organization: Oncode Institute, 3521 AL Utrecht, Netherlands – sequence: 3 givenname: Krijn K orcidid: 0000-0002-5417-5397 surname: Dijkstra fullname: Dijkstra, Krijn K organization: Oncode Institute, 3521 AL Utrecht, Netherlands – sequence: 4 givenname: Chelsea M orcidid: 0000-0002-3548-3482 surname: McLean fullname: McLean, Chelsea M organization: Oncode Institute, 3521 AL Utrecht, Netherlands – sequence: 5 givenname: Sovann surname: Kaing fullname: Kaing, Sovann organization: Oncode Institute, 3521 AL Utrecht, Netherlands – sequence: 6 givenname: Erik orcidid: 0000-0001-7469-7427 surname: van Werkhoven fullname: van Werkhoven, Erik organization: Department of Biometrics, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands – sequence: 7 givenname: Luuk surname: Schipper fullname: Schipper, Luuk organization: Oncode Institute, 3521 AL Utrecht, Netherlands – sequence: 8 givenname: Louisa surname: Hoes fullname: Hoes, Louisa organization: Oncode Institute, 3521 AL Utrecht, Netherlands – sequence: 9 givenname: Daniel J surname: Vis fullname: Vis, Daniel J organization: Department of Molecular Carcinogenesis, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands – sequence: 10 givenname: Joris orcidid: 0000-0001-5899-3971 surname: van de Haar fullname: van de Haar, Joris organization: Department of Molecular Carcinogenesis, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands – sequence: 11 givenname: Warner surname: Prevoo fullname: Prevoo, Warner organization: Department of Radiology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands – sequence: 12 givenname: Petur orcidid: 0000-0002-1086-8108 surname: Snaebjornsson fullname: Snaebjornsson, Petur organization: Department of Pathology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands – sequence: 13 givenname: Daphne orcidid: 0000-0001-9287-1863 surname: van der Velden fullname: van der Velden, Daphne organization: Oncode Institute, 3521 AL Utrecht, Netherlands – sequence: 14 givenname: Michelle orcidid: 0000-0001-9285-991X surname: Klein fullname: Klein, Michelle organization: Oncode Institute, 3521 AL Utrecht, Netherlands – sequence: 15 givenname: Myriam orcidid: 0000-0002-8607-6174 surname: Chalabi fullname: Chalabi, Myriam organization: Department of Molecular Oncology and Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands – sequence: 16 givenname: Henk surname: Boot fullname: Boot, Henk organization: Department of Gastrointestinal Oncology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands – sequence: 17 givenname: Monique orcidid: 0000-0002-5719-3208 surname: van Leerdam fullname: van Leerdam, Monique organization: Department of Gastrointestinal Oncology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands – sequence: 18 givenname: Haiko J surname: Bloemendal fullname: Bloemendal, Haiko J organization: Department of Internal Medicine/Oncology, Radboud University Medical Center Nijmegen, 6525 GA Nijmegen, Netherlands – sequence: 19 givenname: Laurens V surname: Beerepoot fullname: Beerepoot, Laurens V organization: Department of Internal Medicine, Elisabeth-TweeSteden Hospital, 5042 AD Tilburg, Netherlands – sequence: 20 givenname: Lodewyk surname: Wessels fullname: Wessels, Lodewyk organization: Faculty of Electrical Engineering, Mathematics and Computer Science, Delft University of Technology, 2628 CD Delft, Netherlands – sequence: 21 givenname: Edwin surname: Cuppen fullname: Cuppen, Edwin organization: Hartwig Medical Foundation, 1098 XH Amsterdam, Netherlands – sequence: 22 givenname: Hans orcidid: 0000-0002-3077-5582 surname: Clevers fullname: Clevers, Hans organization: Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, Netherlands – sequence: 23 givenname: Emile E orcidid: 0000-0001-8249-9586 surname: Voest fullname: Voest, Emile E email: e.voest@nki.nl organization: Department of Gastrointestinal Oncology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31597751$$D View this record in MEDLINE/PubMed |
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