Researchers have unveiled a publicly available biobank of 256 clinically annotated patient-derived organoids across five cancer types, alongside genome-wide CRISPR screens mapping critical cancer gene dependencies. The resource aims to improve targeted drug discovery and reflect tumor heterogeneity more accurately than traditional cell lines.
Bridging the Gap Between Patient Tumors and Laboratory Models
For decades, cancer research has relied heavily on two-dimensional cell lines grown on flat plastic surfaces. While these workhorse models have driven significant discoveries in targeted therapies, they possess clear limitations. Two-dimensional lines often fail to capture the complex diversity of human tumors and gradually adapt to laboratory conditions over time, losing key characteristics of the original cancers.
To address these shortcomings, researchers at the Wellcome Sanger Institute and collaborative clinical sites in Birmingham, Cambridge, Glasgow, London, and Southampton have generated a specialized biobank of 256 clinically annotated organoids. Described in research published in Nature, the collection covers five cancer types where new treatments are urgently needed: colorectal, esophageal, gastric, pancreatic, and ovarian cancers.
“By building this organoid biobank, which is a long-term resource of cancer models, we’ve created a powerful new way to study cancer in models that much more closely resemble patient tumours. Applying CRISPR screening across these models enabled us to pinpoint the specific genes that different cancers rely on to grow and survive.”
Dr Carmen Herranz-Ors, first author at the Wellcome Sanger Institute
Unlike traditional cell lines, organoids maintain a three-dimensional architecture that mimics the physical and biological structure of actual human tumors. Because the samples are derived directly from fresh patient tissue, they preserve considerably more of the biological heterogeneity found across different patients.
A Decade of International Collaboration and Scale
The newly unveiled organoid collection is part of a broader, decade-long international effort. Following the completion of the Cancer Genome Atlas, which mapped genomic alterations across thousands of patient samples, researchers recognized that roughly 1,000 existing cell lines were insufficient to represent all cancer types, genotypes, and patient ethnicities.
The Human Cancer Models Initiative, launched in 2016 with funding from the National Cancer Institute and the United Kingdom’s Wellcome Trust, sought to expand the global repository of patient-derived models. Across dozens of partnering institutions—including MIT’s Koch Institute, the Broad Institute, the Dana-Farber Cancer Institute, and the National Cancer Institute—nearly 700 new cancer models representing 25 different cancer types have now been established and deposited at the American Type Culture Collection for researchers worldwide.
“Since the sequencing of the human genome and the analysis of cancer genomes over the last 20 years, we have had many ideas about cancer targets, but we need experimental systems in the lab to validate those targets and launch drug discovery projects.”
Jesse Boehm, research scientist at the Koch Institute and senior author
More than 2,700 tumor samples were collected from participating hospitals in the United States, the United Kingdom, and the Netherlands. Every established model underwent rigorous molecular characterization, including whole-genome sequencing, transcriptome sequencing, and the generation of matched normal DNA from each patient to accurately track tumor-specific mutations.
Mapping Cancer Vulnerabilities Through Genome-Wide CRISPR Screening
Beyond establishing the biobank itself, the research team demonstrated that delicate organoid cultures could support genome-wide CRISPR-Cas9 screens at a scale comparable to conventional cell lines.
Screening 162 of the organoid models yielded approximately 1,700 associations between gene dependencies and specific clinical or genomic traits.
The dependency map confirmed established cancer biology while also uncovering vulnerabilities difficult to detect in flat cell cultures. Furthermore, by analyzing organoids grown from the same patient both before and after treatment, researchers were able to observe how tumors develop resistance to therapies while exposing new biological pathways for exploration.
What the Resource Offers the Global Research Community
The genomic datasets, transcriptomic information, clinical annotations, and CRISPR screening results have all been deposited into public repositories. Clinicians and surgical teams emphasize that the close cooperation between patients, clinical sites, and laboratory scientists was essential to capturing the true behavioral complexity of human tumors.
“This work was only possible because of a close collaboration between scientists, clinicians and patients. It gives us a clearer picture of how cancers behave in patients and why responses to treatment can vary, helping to guide more effective patient care.”
Dr Andrew Beggs, Professor of Cancer Genetics and Surgery at the University of Birmingham
Rather than entirely replacing standard two-dimensional cell lines or animal models—the latter of which may see reduced reliance thanks to these 3D cultures—the new biobank serves as a complementary platform. Scientists can now explore the open data repository, identify specific models matching their research questions, and request the physical organoids to test new therapeutic hypotheses and accelerate drug discovery.
