Patient cancer cells help to test treatments
A study, published today in Cell, demonstrates the power of organoids to capture, in three dimensions, the multiple mutations that occur in tumours. Organoids, small clusters of cells that accurately mimic the behaviour of human tissue, can be used to test cancer drugs and, eventually, to identify effective personalised treatments for patients.
Until now, cancer drug screening has primarily been carried out using two-dimensional cell lines grown in dishes, or in mouse models. Organoids, which more closely resemble human tumours than cell lines, and are less time and resource intensive than mouse models, offer researchers a middle ground between existing approaches.
These exciting findings are the result of an international collaboration involving research teams in the UK, Netherlands, and the US.
“Every tumour is different, even those that arise in the same organ. They each have a mixture of cells with different mutations that subsequently determine if a treatment will be effective. Organoids, much to our delight, replicated the features of patient tumours. This gives us a more realistic environment in which to test new and existing drugs, and to explore combination therapies.”
Dr Hayley Francies A first author from the Wellcome Trust Sanger Institute
Researchers at the Hubrecht Institute, The Netherlands, have pioneered the use of organoids, which have important applications in cancer research, stem cell biology and regenerative medicine. The organoids used in the study were derived at the Hubrecht Institute using stem cells from colon tissue. Stem cells, which are found in most tissues, are responsible for growth and repair, so they replicate constantly. When isolated in culture, the cells continue to grow, forming small cell-clusters that retain their tissue identity.
Samples from healthy tissue and cancerous tissue were taken from 20 patients with colorectal carcinoma and used to form the organoids. The organoids were then exposed to a range of colorectal cancer treatments as part of the Sanger Institute’s high-throughput drug screen, which is testing hundreds of different drugs against cancer cell lines.
“This exciting new tool has the potential to transform the way we develop and deliver cancer treatment. We feel fortunate to have been part of this collaborative scientific effort. We are now building a biobank of organoids at the Sanger Institute that will help to illuminate the complex interactions between the multiple genomic alterations in tumours that determine which drugs work and which don’t.”
Dr Mathew Garnett A senior author at the Sanger Institute
Organoids could ultimately be used in the clinic to predict how a patient will respond to treatment. However, researchers say that more work to speed up and standardise the process of producing and testing organoids is needed before this is possible. In the short term, organoids are likely to speed up the process of developing new cancer treatments and reduce costs.
“Often, the jump from studying a cancer treatment in cells to performing a successful patient trial is too wide. Organoids are so experimentally tractable that they can answer many of our questions about cancers, bridging this gap. Not only can organoids save time and resources, we hope that they will one day let us see how treatments will work in an individual’s unique cancer.”
Professor Hans Clevers A senior author at the Hubrecht Institute
More information
Funding
Marc van de Wetering is supported by Stichting Virtutis Opus and Stitchting Vrienden van het Hubrecht. Robert GJ Vries, Sridevi Jaksani and Joyce Blokker are supported by a grant from Alpe dHuzes/KWF. This work was supported with a grant from the Dutch Cancer Society to Michael Stratton (H1/2014-6919).
Participating Centres
Hubrecht Institute, Hubrecht Organoid Technology, Wellcome Trust Sanger Institute, Broad Institute of MIT and Harvard, The Netherlands Cancer Institute, European Molecular Biology Laboratory – European Bioinformatics Institute, Diakonessenhuis, University of Amsterdam, Medical Research Council National Institute for Medical Research.
Publications:
Selected websites
The Hubrecht Institute
The Hubrecht Institute is a research institute of the Royal Netherlands Academy of Arts and Sciences (KNAW). Research at the Hubrecht Institute focuses on developmental biology and stem cells at the organismal, cellular, genetic, genomic and proteomic level. Basic insight into development and into stem cells will provide insight into (human) disease, such as cancer. The Hubrecht Institute is affiliated with the University Medical Center Utrecht and has close connections with the Utrecht University, e.g. in the Cancer, Stem cells & Developmental biology (CS&D) Master’s and PhD programs.
Hubrecht Organoid Technology
Hubrecht Organoid Technology (The HUB) is a not-for-profit organization founded by the Hubrecht Institute, KNAW and University Medical Center Utrecht, the Netherlands. The HUB is founded on the pioneering work of Professor Dr Hans Celvers, who discovered methods to grow stem cell-derived human epithelial ‘mini-organs’ (organoids) from tissues of patients with various diseases including cancer and cystic fibrosis.
Eli and Edythe L. Broad Institute of MIT and Harvard
The Eli and Edythe L. Broad Institute of MIT and Harvard was launched in 2004 to empower this generation of creative scientists to transform medicine. The Broad Institute seeks to describe all the molecular components of life and their connections; discover the molecular basis of major human diseases; develop effective new approaches to diagnostics and therapeutics; and disseminate discoveries, tools, methods, and data openly to the entire scientific community. Founded by MIT, Harvard, and its affiliated hospitals, and the visionary Los Angeles philanthropists Eli and Edythe L. Broad, the Broad Institute includes faculty, professional staff, and students from throughout the MIT and Harvard biomedical research communities and beyond, with collaborations spanning over a hundred private and public institutions in more than 40 countries worldwide.
Netherlands Cancer Institute
The Netherlands Cancer Institute accommodates approximately 650 scientists and scientific support personnel. The Antoni van Leeuwenhoek Hospital has 185 medical specialists, 180 beds, an out-patients clinic that receives 27,000 patients each year, 5 operating theaters and 11 radiotherapy units. It is the only dedicated cancer center in The Netherlands and maintains an important role as a national and international center of scientific and clinical expertise, development and training.
European Bioinformatics Institute
The European Bioinformatics Institute is part of the European Molecular Biology Laboratory (EMBL), Europe’s flagship laboratory for the life sciences. EMBL-EBI provides freely available data from life science experiments covering the full spectrum of molecular biology, and performs investigator-led research using computational approaches to unravel the secrets of life. Our extensive training programme helps researchers in academia and industry to make the most of the incredible amount of data being produced every day in life science experiments. We are a non-profit, intergovernmental organisation funded by EMBL member states. Our 500 staff hail from 43 countries, and we welcome a regular stream of visiting scientists throughout the year.
University of Amsterdam
The University of Amsterdam (UvA) is a broad, research-intensive institution rooted in the history of Amsterdam, an internationally oriented academic community that can compete with leading universities in the Netherlands and around the world. The UvA provides academic training in all areas of science and scholarship, and welcomes students and staff – from all backgrounds, cultures and faiths – who wish to devote their talents to the development and transfer of academic knowledge as a rich cultural resource and foundation for sustainable progress.
Medical Research Council National Institute for Medical Research
The Medical Research Council National Institute for Medical Research is a research institute dedicated to studying important questions about the life processes that are relevant to all aspects of health. The Institute is the largest supported by the Medical Research Council(MRC), a national organisation funded by the British taxpayer that promotes research into all areas of medical and related science to improve the health of the British public. Our mission is to carry out innovative high quality biomedical research; to be a major contributor to the MRC’s commitments in the training of scientists and to present our science to the public.
The Wellcome Trust Sanger Institute
The Wellcome Trust Sanger Institute is one of the world’s leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease.
The Wellcome Trust
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests.
Garnett Group
The Translational Cancer Genomics team explores how abnormalities in the DNA of cells contribute to cancer and impact on patient responses to therapy. This provides fundamental insights into disease mechanisms with implications for the development of improved therapies.
Dr Hayley Francies
Within the Translational Cancer Genomics group, Hayley’s work is focused upon the derivation and use of 3D cancer organoid models for genomic analyses and drug screens to identify novel cancer therapies and genetic biomarkers of drug response.
Dr Mathew Garnett
Mathew investigates how genetic alterations contribute to cancer and impact on patient responses to anti-cancer medicines. This work provides fundamental insights into cancer biology with direct links to the development of new cancer therapies.
