A new open resource of patient-derived cancer models has enabled researchers to create the first large-scale map of the genes that cancers rely on to survive, according to an Aug. 5 announcement. The project aims to offer new routes for research into better and less toxic treatments for patients.
The work, published in Nature by researchers from the Wellcome Sanger Institute and collaborators across five clinical sites in the UK, centers on a large biobank of tumor models known as organoids. This biobank is designed to help scientists identify genes that specific cancers depend on for growth, revealing potential weak points that could be targeted with future treatments. The study is published alongside two complementary papers from international collaborators as part of a multi-year effort to refine organoid models and make them more accessible.
Traditionally, cancer research has relied on two-dimensional cell lines grown in laboratory plates. While these have provided important insights into cancer biology, they do not fully capture the diversity and complexity of tumors seen in patients. Organoids are next-generation models developed from patient tumors that more closely reflect real-life tumor characteristics.
To build the biobank, researchers partnered with clinicians at hospital sites in Birmingham, Cambridge, Glasgow, London and Southampton. Fresh tumor samples donated by consenting patients were sent to the Sanger Institute, where 256 organoids were developed across colorectal, esophageal, pancreatic, stomach and ovarian cancers. DNA sequencing was performed on these organoids as well as blood samples and original tumors when available.
Using CRISPR screening across 162 organoid models allowed researchers to systematically switch off genes one by one and observe which ones were critical for cancer cell survival. Thousands of genetic dependencies were identified—some common among many cancers and others specific to certain tumor types. By combining this data with genomic and clinical information, 1,733 links between genetic dependencies and features such as DNA changes or treatment history were found.
Dr. Carmen Herranz-Ors at the Wellcome Sanger Institute said, “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 tumors. Applying CRISPR screening across these models enabled us to pinpoint the specific genes that different cancers rely on to grow and survive.”
Dr. Catherine Elliott at Cancer Research UK said, “Organoids give scientists the ability to study cancer in richer detail, giving them new insights into its weak spots. Research like this brings us closer to new treatments and with that the hope of more people living longer, better lives.”
Dr. Andrew Beggs at University of Birmingham said, “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...” Dr. Mathew Garnett at Wellcome Sanger Institute added, “This study brings together patient-derived cancer models...at a scale that has not previously been possible...and creates a resource that the wider research community can build on.”
