Start-Up of Human Cancer Models Initiative

An international collaboration to develop the next-generation of cancer cell models as a resource for the scientific community

The Human Cancer Model Initiative debuts in July 2016 as an international effort to develop the next-generation of cancer cell models that better represent the hallmarks and diversity of human cancers. Four partners take a leadership role in this collaborative initiative: Wellcome Trust Sanger Institute in Cambridge, UK, the Cancer Research UK (CRUK), the US National Cancer Institute (NCI), and the foundation Hubrecht Organoid Technology (HUB) in Utrecht, the Netherlands. The researchers will derive and genetically characterise new organoid models and make them available to researchers as a transformative resource for the community. 

Approximately 1,000 human cancer cell lines are available to scientists worldwide and these are a useful resource for cancer research and drug development. These cell lines have been used extensively for modelling drug response to identify molecular alterations in cancer which impact on drug sensitivity. This information can be used to understand the variation observed in patient responses to treatment and to help guide the development of new more effective and less toxic cancer therapies.

However, as we enter the era of precision cancer medicine, treating molecularly defined patients, poor representation of some cancer types, insufficient numbers to capture the genetic diversity of cancer, lack of clinical outcome data and lack of comparison to normal reference sample limit the use of the current set of cell lines. Novel cell culturing methods such as organoid derivation have revolutionised researchers’ ability to derive cell line models from both healthy and diseased tissue, and have the potential to overcome these limitations.

Organoids are a long-term culture system which allow cells to be grown in specialised 3D culture conditions that maintain the stem cell population as well as much of the cell/tissue architecture found in vivo. Cancer organoid models have been shown to recapitulate features of the original tissue/tumour and can model clinically relevant drug responses. 

As part of the initiative, the researchers will join forces to make around 1,000 cancer cell models. The cancer models will closely mirror the cellular complexity and architecture of human tumours, and are being developed using new cell culture techniques, such as those that enable efficient production of conditionally reprogrammed cells and organoids. They will be generated using tumour tissue from patients with a variety of cancer types, including rare and paediatric cancers which are often underrepresented or absent from existing cell line collections.

The originating tumour and the derived models will be sequenced, and this information, as well as patient-pertinent clinical data, will be available to researchers. The project will empower researchers to study many aspects of cancer, including tumour heterogeneity, disease progression, mechanisms of drug resistance, and the development of precision medicine treatments.

The Wellcome Trust Sanger Institute has joined forces with CRUK to derive approximately 250 organoid cell models from colon, oesophageal and pancreatic cancers. These models are being generated from patient samples taken at the time of surgical resection and will include a subset of patient-matched normal organoid models. CRUK have provided access to their unique clinical network allowing access to clinical samples as well as the collection of clinical data.

These models will be derived at the Sanger Institute and will be highly annotated including a complete sample history and key patient clinical information. The original tumour as well as the matched organoid culture will also be genomically characterised and drug screens performed. These new cell models and associated datasets will be shared with the research community to further research.

As part of a pilot phase, over the next two years the Sanger Institute and CRUK will critically evaluate the utility of organoids as cancer models by addressing the following questions: 

  • How does organoid derivation compare with other cell derivation methods?
  • Are organoid cultures genetically and phenotypically stable in cultures over time?
  • How well do organoid cultures capture genetic changes observed in patients?
  • Are organoids a useful tool for modelling drug response observed clinically?
  • Can we develop the infrastructure and improve derivation processes to increase success rates and reduce costs?

CRUK is co-funding organoid derivation together with the Sanger Institute. CRUK has leveraged their unique network of clinical sites allowing to access clinical samples and to work with world-leading researchers. 

The HUB is a not-for-profit organisation founded by the Royal Netherlands Academy of Sciences and the University Medical Center Utrecht. The HUB exploits the pioneering work of Prof. Hans Clevers, who discovered methods to grow stem cell-derived human organoids from tissues of patients with various diseases. The HUB is deriving hundreds of cancer organoid models as part of the Human Cancer Model Initiative.

The US NCI will be funding multiple research groups to derive cancer cell models as part of the Human Cancer Model Initiative.

The findings will help establish the utility of organoids as a model system for studying cancer and could pave the way for derivation of an even larger number of models to encompass the genetic diversity of cancer.

The initiative will provide the research community with the next-generation of cancer cell models and by working together will accelerate this process in a cost-effective, streamlined and unified way, allowing for rapid learning, protocol sharing and standardised practices while avoiding duplication of efforts.