Peer-reviewedCC BYNature
A tumour-derived organoid biobank maps cancer gene dependencies
9 affiliations
- 1Wellcome Sanger Institute, Cambridge, UK
- 2European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge, UK
- 3Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK
- 4AstraZeneca, The Discovery Centre (DISC), Cambridge, UK
- 5Instituto de Investigación Biomédica A Coruña (INIBIC), A Coruña, Spain
- 6University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- 7Early Cancer Institute, University of Cambridge, Cambridge, UK
- 8Department of Surgery and Cancer, Imperial College London, London, UK
- 9Institute of Immunology and Immunotherapy, College of Medical and Dental Science, University of Birmingham, Birmingham, UK
Abstract
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 lines 1 . 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.
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BibTeX
@article{herranzors2026tumourderived,
title = {{A tumour-derived organoid biobank maps cancer gene dependencies}},
author = {Carmen Herranz‐Ors and Shriram G. Bhosle and A. E. Beck and James G. R. Gilbert and Gabriele Picco and Jose Espejo Valle-Inclán and Francesc Muyas and S. Valentini and A. E. Andres and R. Ansari and Syd Barthorpe and G. Battarbee and Charlotte Beaver and S. Brocklesby and J. Cantwell and C. A. Collins and J. Davis and Hristina Grigorova Dimitrova and J. Doran and E. Efendi and K. Evans and Mya Fekry-Troll and T. A. Fowler and M. Garcia-Casado and J. A. T. Griffiths and C. Hall and R. Hamer and C. Hardy and Zoe Hewitson and Emma Hitch and L. Holland and D. A. JACKSON and N. Joshi and Anastasia Kavasakali and L. Letchford and H. B. Lightfoot and H. Lingala and I. Mali and Kieron May and Tatiana Mironenko and J. Morris and Clare Pacini and S. Price and G. Robert-Tissot and H. A. Rogers and J. V. Smith and K. Smith and E. Souster and W. J. Spence and F. Thomas and Sara F. Vieira and S. Walker and G. Alfonsin and H. Bermingham and H. Coles and Darren P. Ennis and Adam Freeman and Gaia Giannone and Nicola Grehan and Ewen Alexander Griffiths},
journal = {Nature},
year = {2026},
month = aug,
doi = {10.1038/s41586-026-10830-y},
url = {https://doi.org/10.1038/s41586-026-10830-y},
note = {CC BY},
}
RIS
TY - JOUR
TI - A tumour-derived organoid biobank maps cancer gene dependencies
AU - Carmen Herranz‐Ors
AU - Shriram G. Bhosle
AU - A. E. Beck
AU - James G. R. Gilbert
AU - Gabriele Picco
AU - Jose Espejo Valle-Inclán
AU - Francesc Muyas
AU - S. Valentini
AU - A. E. Andres
AU - R. Ansari
AU - Syd Barthorpe
AU - G. Battarbee
AU - Charlotte Beaver
AU - S. Brocklesby
AU - J. Cantwell
AU - C. A. Collins
AU - J. Davis
AU - Hristina Grigorova Dimitrova
AU - J. Doran
AU - E. Efendi
AU - K. Evans
AU - Mya Fekry-Troll
AU - T. A. Fowler
AU - M. Garcia-Casado
AU - J. A. T. Griffiths
AU - C. Hall
AU - R. Hamer
AU - C. Hardy
AU - Zoe Hewitson
AU - Emma Hitch
AU - L. Holland
AU - D. A. JACKSON
AU - N. Joshi
AU - Anastasia Kavasakali
AU - L. Letchford
AU - H. B. Lightfoot
AU - H. Lingala
AU - I. Mali
AU - Kieron May
AU - Tatiana Mironenko
AU - J. Morris
AU - Clare Pacini
AU - S. Price
AU - G. Robert-Tissot
AU - H. A. Rogers
AU - J. V. Smith
AU - K. Smith
AU - E. Souster
AU - W. J. Spence
AU - F. Thomas
AU - Sara F. Vieira
AU - S. Walker
AU - G. Alfonsin
AU - H. Bermingham
AU - H. Coles
AU - Darren P. Ennis
AU - Adam Freeman
AU - Gaia Giannone
AU - Nicola Grehan
AU - Ewen Alexander Griffiths
PY - 2026
DA - 2026/08/05
JO - Nature
DO - 10.1038/s41586-026-10830-y
UR - https://doi.org/10.1038/s41586-026-10830-y
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 lines 1 . 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.
SN - 0028-0836
SN - 1476-4687
ER -