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

被引：491

作者：

Ooft, Salo N. ^{[1
,2
]}

Weeber, Fleur ^{[1
,2
]}

Dijkstra, Krijn K. ^{[1
,2
]}

McLean, Chelsea M. ^{[1
,2
]}

Kaing, Sovann ^{[1
,2
]}

van Werkhoven, Erik ^{[3
]}

Schipper, Luuk ^{[1
,2
]}

Hoes, Louisa ^{[1
,2
]}

Vis, Daniel J. ^{[2
,4
]}

van de Haar, Joris ^{[1
,2
,4
]}

Prevoo, Warner ^{[5
]}

Snaebjornsson, Petur ^{[6
]}

van der Velden, Daphne ^{[1
,2
,16
]}

Klein, Michelle ^{[1
,2
]}

Chalabi, Myriam ^{[1
]}

Boot, Henk ^{[7
]}

van Leerdam, Monique ^{[7
]}

Bloemendal, Haiko J. ^{[8
]}

Beerepoot, Laurens V. ^{[9
]}

Wessels, Lodewyk ^{[2
,4
,10
]}

Cuppen, Edwin ^{[2
,11
,12
]}

Clevers, Hans ^{[2
,13
,14
,15
]}

Voest, Emile E. ^{[1
,2
,7
]}

机构：

[1] Netherlands Canc Inst, Dept Mol Oncol & Immunol, NL-1066 CX Amsterdam, Netherlands

[2] Oncode Inst, NL-3521 AL Utrecht, Netherlands

[3] Netherlands Canc Inst, Dept Biometr, NL-1066 CX Amsterdam, Netherlands

[4] Netherlands Canc Inst, Dept Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

[5] Netherlands Canc Inst, Dept Radiol, NL-1066 CX Amsterdam, Netherlands

[6] Netherlands Canc Inst, Dept Pathol, NL-1066 CX Amsterdam, Netherlands

[7] Netherlands Canc Inst, Dept Gastrointestinal Oncol, NL-1066 CX Amsterdam, Netherlands

[8] Radboud Univ Nijmegen, Dept Internal Med Oncol, Med Ctr Nijmegen, NL-6525 GA Nijmegen, Netherlands

[9] Elisabeth TweeSteden Hosp, Dept Internal Med, NL-5042 AD Tilburg, Netherlands

[10] Delft Univ Technol, Fac Elect Engn Math & Comp Sci, NL-2628 CD Delft, Netherlands

[11] Univ Med Ctr Utrecht, Ctr Mol Med, Div Biomed Genet, NL-3584 CX Utrecht, Netherlands

[12] Hartwig Med Fdn, NL-1098 XH Amsterdam, Netherlands

[13] Royal Netherlands Acad Arts & Sci, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands

[14] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands

[15] Princess Maxima Ctr Pediat Oncol, NL-3584 CS Utrecht, Netherlands

[16] Amsterdam Univ Med Ctr AMC, Dept Radiol & Nucl Med, NL-1105 AZ Amsterdam, Netherlands

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2019年 / 11卷 / 513期

关键词：

THYMIDYLATE SYNTHASE EXPRESSION; CLINICAL PHARMACOKINETICS; FLUOROURACIL; OXALIPLATIN; RESISTANCE; QUANTITATION; SENSITIVITY; LANDSCAPE; THERAPY;

D O I：

10.1126/scitranslmed.aay2574

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：9

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