Organoids, miniature tumours grown in the lab from cancer patients, could become a powerful weapon - first for oncology research and then in clinical practice to optimise therapy. A collaboration between the Hubrecht Institute in the Netherlands, the UK's Sanger Institute and the Broad Institute in the US has shown that microscopic organoids provide a good 3D representation of individual colorectal tumours for testing anti-cancer drugs. The study is published in the journal Cell.
"This is the first time that a collection of cancer organoids, or a living biobank, has been derived from patient tumours," says senior author Matthew Garnett. "We believe that these organoids are an important new tool in the arsenal of cancer biologists."
Every tumour has a different mixture of cells with different mutations that influence the future course and treatment of the disease. "Organoids, much to our delight, replicated the features of patient tumours," adds Hayley Francies of the Sanger Institute. "This gives us a more realistic environment in which to test new and existing drugs and to explore combination therapies."
Organoids represent something of a halfway house between the two main methods used today to test cancer treatments. Their 3D structure makes organoids a more realistic representation than two-dimensional tumour cell lines grown in lab dishes, while their relative simplicity avoids the cost and complexity of growing tumours in mice.
Researchers at the Hubrecht Institute produced organoids from stem cells extracted from 20 people with colorectal cancer. Special culture conditions enabled them to divide and grow into microscopic 3D clusters of a few hundred cells each, which retained the identity of the originating tissue. Genetic mutations in each organoid closely matched those in DNA from the patient's direct tumour biopsy.
The Sanger Institute's drug-screening lab then exposed the colorectal organoids to a range of 83 experimental and approved cancer treatments. They showed a range of sensitivities to different drugs, depending on their genetic make-up. It revealed one previously unknown drug-gene association: patients with RNF43 mutations would benefit from a drug that targets a protein called porcupine.
Sanger scientists are now building an organoid biobank, starting with colorectal cancer and then moving on to other tumour types. "Cancer is a diverse and complex disease and having a large collection of organoids is necessary to encompass this diversity to enable scientists and clinicians to develop new treatments," Garnett says.
Photograph: Marc van de Wetering, Hubrecht Institute for Developmental Biology
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