University of Birmingham contributes to new biobank of tumour models which reveal cancer weaknesses

Researchers from the University of Birmingham have supported the development of a new open resource of patient-derived tumour organoids. The collection - which is the largest of its kind to date - will help researchers to identify the genes that particular cancers require for growth and highlight potential weaknesses which could be targeted with treatment.

Published today in Nature, researchers from the Wellcome Sanger Institute collaborated with five clinical sites across the UK, including the University of Birmingham, to develop the new large biobank of tumour models (known as organoids).

Biobanks, also known as “bioresources” or “research tissue banks”, collect, store and release biological material. This may include blood or tissue from humans, soil samples, bacteria, plants, strands of DNA, or several other types of biological material.

The University of Birmingham’s Human Biomaterials Resource Centre (HBRC) was one of five clinical sites which collected fresh tumour samples donated by consenting patients to build the new biobank, which were then sent to the Wellcome Sanger Institute where the organoids derived and genes were mapped.

The HBRC is a biobank itself, which approaches healthy volunteers and NHS patients for samples and data to be used in scientific research. Biobanks like the HBRC are called “generic” biobanks – meaning that they are not restricted to particular diseases or samples.

Instead, they seek to help as many areas of scientific research as is practical by accepting human material and medical data about almost any disease or condition. Generic biobanks are an easy way for patients to support new research into their disease or condition, because leftover material is being utilised when otherwise it might have been discarded.

Dr Andrew Beggs, Professor of Cancer Genetics and Surgery and lead the study site at the 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 and why responses to treatment can vary, helping to guide more effective patient care.”

In the study, researchers aimed to create a large biobank of organoids - miniaturised, 3D tissue cultures grown in the lab, replicating the complex structures and specific functions of five cancer types which need new treatments; namely colorectal, oesophageal, ovarian, pancreatic and stomach cancers.

This is a step change from the long-relied-upon 2D cell lines used to study cancer, which have several limitations that make them less suitable to model new treatments of cancer. In addition, organoid models can replace the need for mouse models, meaning a significant reduction in animal testing can be achieved.

Dr Carmen Herranz-Ors, first author 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 tumours. Applying CRISPR screening across these models enabled us to pinpoint the specific genes that different cancers rely on to grow and survive.”

Using these vital donations from the HBRC and other clinical sites in Cambridge, Glasgow, London and Southampton, researchers at the Wellcome Sanger Institute developed 256 organoids from the five cancer types and sequenced DNA from the organoids, patient blood samples and the original tumours to create a reference resource, the most detailed of its kind. This resource allows researchers to track and monitor any changes to the organoids over time as they grow.

The team were also able to identify thousands of genetic dependencies, including genes required to survive and weaknesses linked to specific tumours. These revealed new insights into how different cancers rely on specific molecular interactions, how tumours develop resistance to treatments, and potential new vulnerabilities which could be used to explore new treatment options.