Patient-derived organoids model treatment response of metastatic gastrointestinal cancers

被引：1514

作者：

Vlachogiannis, Georgios ^{[1
]}

Hedayat, Somaieh ^{[1
]}

Vatsiou, Alexandra ^{[2
]}

Jamin, Yann ^{[3
,4
]}

Fernandez-Mateos, Javier ^{[1
,2
]}

Khan, Khurum ^{[1
,5
]}

Lampis, Andrea ^{[1
]}

Eason, Katherine ^{[1
]}

Huntingford, Ian ^{[1
]}

Burke, Rosemary ^{[6
]}

Rata, Mihaela ^{[3
,4
]}

Koh, Dow-Mu ^{[3
,4
,7
]}

Tunariu, Nina ^{[3
,4
,7
]}

Collins, David ^{[3
,4
]}

Hulkki-Wilson, Sanna ^{[1
]}

Ragulan, Chanthirika ^{[1
]}

Spiteri, Inmaculada ^{[2
]}

Moorcraft, Sing Yu ^{[5
]}

Chau, Ian ^{[5
]}

Rao, Sheela ^{[5
]}

Watkins, David ^{[5
]}

Fotiadis, Nicos ^{[7
]}

Bali, Maria ^{[3
,4
,7
]}

Darvish-Damavandi, Mahnaz ^{[1
]}

Lote, Hazel ^{[1
,5
]}

Eltahir, Zakaria ^{[1
]}

Smyth, Elizabeth C. ^{[5
]}

Begum, Ruwaida ^{[5
]}

Clarke, Paul A. ^{[6
]}

Eltahir, Zakaria ^{[1
]}

Smyth, Elizabeth C. ^{[5
]}

Begum, Ruwaida ^{[5
]}

Clarke, Paul A. ^{[6
]}

Hahne, Jens C. ^{[1
]}

Dowsett, Mitchell ^{[8
]}

de Bono, Johann ^{[9
]}

Workman, Paul ^{[6
]}

Sadanandam, Anguraj ^{[1
]}

Fassan, Matteo ^{[10
]}

Sansom, Owen J. ^{[11
]}

Eccles, Suzanne

Starling, Naureen ^{[5
]}

Braconi, Chiara ^{[5
,6
]}

Sottoriva, Andrea ^{[2
]}

Robinson, Simon P. ^{[3
,4
]}

Cunningham, David ^{[5
]}

Valeri, Nicola ^{[1
,5
]}

机构：

[1] Inst Canc Res, Div Mol Pathol, London, England

[2] Inst Canc Res, Ctr Evolut & Canc, London, England

[3] Inst Canc Res, Canc Res UK Canc Imaging Ctr, Div Radiotherapy & Imaging, London, England

[4] Royal Marsden Hosp, London, England

[5] Royal Marsden NHS Trust, Dept Med, London, England

[6] Inst Canc Res, Canc Res UK Canc Therapeut Unit, London, England

[7] Royal Marsden NHS Trust, Dept Radiol, London, England

[8] Royal Marsden NHS Trust, Ralph Lauren Ctr Breast Canc Res, London, England

[9] Inst Canc Res, Div Clin Studies, London, England

[10] Univ Padua, Surg Pathol & Cytopathol Unit, Dept Med, Padua, Italy

[11] Canc Res UK Beatson Inst, Glasgow, Lanark, Scotland

来源：

SCIENCE | 2018年 / 359卷 / 6378期

基金：

英国惠康基金;

关键词：

COMPREHENSIVE MOLECULAR CHARACTERIZATION; COLORECTAL-CANCER; PRECISION MEDICINE; THERAPY; TAS-102; TRIAL;

D O I：

10.1126/science.aao2774

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from metastatic, heavily pretreated colorectal and gastroesophageal cancer patients recruited in phase 1/2 clinical trials. Phenotypic and genotypic profiling of PDOs showed a high degree of similarity to the original patient tumors. Molecular profiling of tumor organoids was matched to drug-screening results, suggesting that PDOs could complement existing approaches in defining cancer vulnerabilities and improving treatment responses. We compared responses to anticancer agents ex vivo in organoids and PDO-based orthotopic mouse tumor xenograft models with the responses of the patients in clinical trials. Our data suggest that PDOs can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs.

引用

页码：920 / +

页数：7

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