Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.
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ICR Authors
Hedayat-Husseyin, Somaieh
Jamin, Yann
Lampis, Andrea
Eason, Katherine
Burke, Rosemary
Rata, Mihaela
Koh, Dow-mu
Tunariu, Nina
Collins, David
Ragulan, Chanthirika
Spiteri Sagastume, Maria
Lote, Hazel
Hahne, Jens
Dowsett, Mitch
De Bono, Johann
Workman, Paul
Sadanandam, Anguraj
Braconi, Chiara
Sottoriva, Andrea
Robinson, Simon
Valeri, Nicola
Jamin, Yann
Lampis, Andrea
Eason, Katherine
Burke, Rosemary
Rata, Mihaela
Koh, Dow-mu
Tunariu, Nina
Collins, David
Ragulan, Chanthirika
Spiteri Sagastume, Maria
Lote, Hazel
Hahne, Jens
Dowsett, Mitch
De Bono, Johann
Workman, Paul
Sadanandam, Anguraj
Braconi, Chiara
Sottoriva, Andrea
Robinson, Simon
Valeri, Nicola
Authors
Vlachogiannis, G
Hedayat, S
Vatsiou, A
Jamin, Y
Fernández-Mateos, J
Khan, K
Lampis, A
Eason, K
Huntingford, I
Burke, R
Rata, M
Koh, D-M
Tunariu, N
Collins, D
Hulkki-Wilson, S
Ragulan, C
Spiteri, I
Moorcraft, SY
Chau, I
Rao, S
Watkins, D
Fotiadis, N
Bali, M
Darvish-Damavandi, M
Lote, H
Eltahir, Z
Smyth, EC
Begum, R
Clarke, PA
Hahne, JC
Dowsett, M
de Bono, J
Workman, P
Sadanandam, A
Fassan, M
Sansom, OJ
Eccles, S
Starling, N
Braconi, C
Sottoriva, A
Robinson, SP
Cunningham, D
Valeri, N
Hedayat, S
Vatsiou, A
Jamin, Y
Fernández-Mateos, J
Khan, K
Lampis, A
Eason, K
Huntingford, I
Burke, R
Rata, M
Koh, D-M
Tunariu, N
Collins, D
Hulkki-Wilson, S
Ragulan, C
Spiteri, I
Moorcraft, SY
Chau, I
Rao, S
Watkins, D
Fotiadis, N
Bali, M
Darvish-Damavandi, M
Lote, H
Eltahir, Z
Smyth, EC
Begum, R
Clarke, PA
Hahne, JC
Dowsett, M
de Bono, J
Workman, P
Sadanandam, A
Fassan, M
Sansom, OJ
Eccles, S
Starling, N
Braconi, C
Sottoriva, A
Robinson, SP
Cunningham, D
Valeri, N
Document Type
Journal Article
Date
2018-02-23
Date Accepted
2018-01-11
Abstract
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.
Citation
Science (New York, N.Y.), 2018, 359 (6378), pp. 920 - 926
Source Title
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
ISSN
0036-8075
eISSN
1095-9203
Research Team
Signal Transduction & Molecular Pharmacology
Gastrointestinal Cancers Clinical Trials
Medicine (RMH Smith Cunningham)
Prostate Cancer Targeted Therapy Group
Endocrinology
Evolutionary Genomics & Modelling
Functional Genomics
Gastrointestinal Cancer Biology and Genomics
Systems and Precision Cancer Medicine
Pre-Clinical MRI
Hit Discovery & Structural Design
Gastrointestinal Cancers Clinical Trials
Medicine (RMH Smith Cunningham)
Prostate Cancer Targeted Therapy Group
Endocrinology
Evolutionary Genomics & Modelling
Functional Genomics
Gastrointestinal Cancer Biology and Genomics
Systems and Precision Cancer Medicine
Pre-Clinical MRI
Hit Discovery & Structural Design