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@article{Herranz-Ors:2026:10.1038/s41586-026-10830-y,
author = {Herranz-Ors, C and Bhosle, SG and Beck, AE and Gilbert, JGR and Picco, G and Espejo, Valle-Inclan J and Muyas, F and Valentini, S and Andres, AE and Ansari, R and Barthorpe, S and Battarbee, G and Beaver, CM and Brocklesby, S and Cantwell, J and Collins, CA and Davis, J and Dimitrova, HG and Doran, J and Efendi, E and Evans, K and Fekry, M and Fowler, TA and Garcia-Casado, M and Griffiths, JAT and Hall, C and Hamer, R and Hardy, C and Hewitson, Z and Hitch, E and Holland, L and Jackson, DA and Joshi, N and Kavasakali, A and Letchford, L and Lightfoot, HB and Lingala, H and Mali, I and May, K and Mironenko, T and Morris, J and Pacini, C and Price, S and Robert-Tissot, G and Rogers, HA and Smith, JV and Smith, K and Souster, E and Spence, WJ and Thomas, F and Vieira, SF and Walker, S and Alfonsin, G and Bermingham, H and Coles, H and Ennis, DP and Freeman, A and Giannone, G and Grehan, N and Griffiths, EA and Hall, J and Lee, SL and Leung, EYL and Loreno, C and Millington, C and Mirnezam},
doi = {10.1038/s41586-026-10830-y},
journal = {Nature},
title = {A tumour-derived organoid biobank maps cancer gene dependencies.},
url = {http://dx.doi.org/10.1038/s41586-026-10830-y},
year = {2026}
}
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TY  - JOUR
AB  - Cancer cell lines remain foundational for research and drug discovery, yet they incompletely capture tumour diversity, lack linked patient context, and have undergone adaptation to culture. Tumour organoids are three-dimensional cultures derived from patient tissue that offer a powerful complement to cell lines1. Here we derived and characterized 256 clinically annotated tumour organoids directly from colorectal, oesophageal, ovarian, pancreatic and gastric cancers as renewable, genetically stable models. Extensive characterization of each model and matched patient tumour samples included whole-genome and transcriptome sequencing, and genome-wide CRISPR-Cas9 screens across 162 organoids mapped gene dependencies. Integrative analyses revealed genomic and clinical markers of dependency across common and rare subtypes, identified organoid-specific essential genes, and revealed targetable vulnerabilities following tumour evolution in paired pre- and post-treatment samples. In colorectal cancer, functional and pharmacological interrogation of the EGFR-RAS-MAPK axis uncovered differential effects of KRAS variant alleles. This open, publicly available resource provides a systematic map of gene dependencies in patient-derived organoids, expanding the model diversity and mechanistic insight needed to advance precision oncology.
AU  - Herranz-Ors,C
AU  - Bhosle,SG
AU  - Beck,AE
AU  - Gilbert,JGR
AU  - Picco,G
AU  - Espejo,Valle-Inclan J
AU  - Muyas,F
AU  - Valentini,S
AU  - Andres,AE
AU  - Ansari,R
AU  - Barthorpe,S
AU  - Battarbee,G
AU  - Beaver,CM
AU  - Brocklesby,S
AU  - Cantwell,J
AU  - Collins,CA
AU  - Davis,J
AU  - Dimitrova,HG
AU  - Doran,J
AU  - Efendi,E
AU  - Evans,K
AU  - Fekry,M
AU  - Fowler,TA
AU  - Garcia-Casado,M
AU  - Griffiths,JAT
AU  - Hall,C
AU  - Hamer,R
AU  - Hardy,C
AU  - Hewitson,Z
AU  - Hitch,E
AU  - Holland,L
AU  - Jackson,DA
AU  - Joshi,N
AU  - Kavasakali,A
AU  - Letchford,L
AU  - Lightfoot,HB
AU  - Lingala,H
AU  - Mali,I
AU  - May,K
AU  - Mironenko,T
AU  - Morris,J
AU  - Pacini,C
AU  - Price,S
AU  - Robert-Tissot,G
AU  - Rogers,HA
AU  - Smith,JV
AU  - Smith,K
AU  - Souster,E
AU  - Spence,WJ
AU  - Thomas,F
AU  - Vieira,SF
AU  - Walker,S
AU  - Alfonsin,G
AU  - Bermingham,H
AU  - Coles,H
AU  - Ennis,DP
AU  - Freeman,A
AU  - Giannone,G
AU  - Grehan,N
AU  - Griffiths,EA
AU  - Hall,J
AU  - Lee,SL
AU  - Leung,EYL
AU  - Loreno,C
AU  - Millington,C
AU  - Mirnezami,A
AU  - Nutzinger,B
AU  - Orzechowska,K
AU  - Pinna,CMA
AU  - Redmond,AM
AU  - Roberts,K
AU  - Roy,S
AU  - Sanders,DA
AU  - Taniere,P
AU  - Vias,M
AU  - Wanigasooriya,K
AU  - OCCAMS,Consortium
AU  - Stratton,MR
AU  - Staudt,LM
AU  - McDermott,U
AU  - Brenton,JD
AU  - McNeish,IA
AU  - Biankin,A
AU  - Sansom,OJ
AU  - Cortes-Ciriano,I
AU  - Underwood,TJ
AU  - Fitzgerald,RC
AU  - Beggs,AD
AU  - Francies,HE
AU  - Garnett,MJ
DO  - 10.1038/s41586-026-10830-y
PY  - 2026///
TI  - A tumour-derived organoid biobank maps cancer gene dependencies.
T2  - Nature
UR  - http://dx.doi.org/10.1038/s41586-026-10830-y
UR  - https://www.ncbi.nlm.nih.gov/pubmed/42557320
ER  -
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