New Biobank of Tumor Models Exposes Cancer’s Weaknesses

Researchers at the Wellcome Sanger Institute and five UK clinical sites published a large-scale map of cancer gene dependencies in Nature on August 5, utilizing a new biobank of 256 patient-derived organoid models across colorectal, oesophageal, pancreatic, stomach, and ovarian cancers. According to Dr Carmen Herranz-Ors, first author at the Wellcome Sanger Institute, building this biobank has created a powerful new way to study cancer in models that closely resemble patient tumours and pinpoint specific survival genes using CRISPR screening.

Organoid Biobank Complements Traditional 2D Cell Lines

For decades, cancer researchers relied on two-dimensional cell lines grown in flat layers on laboratory plates. While these models provided vital insights, they fail to fully capture tumour diversity and complexity, having adapted to laboratory conditions over time. To bridge this gap, researchers partnered with clinicians across UK hospital sites in Birmingham, Cambridge, Glasgow, London, and Southampton to collect fresh tumour samples from consenting patients, according to study details.

The team at the Wellcome Sanger Institute isolated these cells and cultured 256 organoid models across five cancer types. By sequencing DNA from the organoids, patient blood samples, and original tumours, the researchers established a deeply characterized reference resource. This lets scientists benchmark the models directly against original patient tumors and track changes during long-term growth.

CRISPR Screening Identifies Thousands of Genetic Dependencies

In a first-of-its-kind study using organoids, researchers applied CRISPR screening across 162 of the models to systematically switch off genes one by one, mapping the biological drivers critical for cancer cell survival. According to the study findings, the team identified thousands of genetic dependencies, separating common survival genes required by many cancers from specific vulnerabilities unique to individual tumour types.

Combining these functional screens with genomic and clinical information revealed 1,733 distinct links between genetic dependencies and specific features like DNA alterations or treatment history. Dr Mathew Garnett, senior author at the Wellcome Sanger Institute, noted that this study brings together patient-derived models, genomics, and functional screening at a scale that has not previously been possible in organoids, creating a resource for the wider research community.

Clinical Collaboration Uncovers Therapy Resistance Pathways

Comparing organoids grown from the same patient before and after treatment allowed researchers to observe how tumours develop resistance to therapy, uncovering potential new weaknesses for alternative treatment approaches. Dr Andrew Beggs, Professor of Cancer Genetics and Surgery at the University of Birmingham, stated that this work was only possible through close collaboration between scientists, clinicians, and patients, providing a clearer picture of variable treatment responses.

Dr Catherine Elliott, Director of Research at Cancer Research UK, added that organoids give scientists the ability to study cancer in richer detail, bringing researchers closer to new treatments and the hope of longer, better lives free from the fear of cancer.

Frequently Asked Questions

What are cancer organoids?

Cancer organoids are patient-derived cell cultures grown in the laboratory that mimic the architecture, heterogeneity, and genetic profile of actual human tumours much more closely than traditional 2D cell lines.

How does CRISPR screening work in these models?

Researchers use CRISPR screening to systematically deactivate genes one at a time within the organoid models, observing whether the cancer cells survive to determine which specific genes are vital for tumor growth.

Which cancer types were included in the biobank?

The new biobank focuses on five cancer types where new treatments are needed: colorectal, oesophageal, pancreatic, stomach, and ovarian cancers.