Using tumor tissue from cancer patients, researchers have grown miniature colons that have successfully replicated key properties of the original tumors. These stand-ins could be incredibly useful one day for testing out drugs and experimenting with treatments to find the best tailored fit for patients. The work is described in Cell this week.
It’s been challenging to predict the drug sensitivity of individual patients, each with their unique genetic mutations. While many labs use experimental models created from cells grown using a patient's cancerous tissue, these currently available, tumor-derived cell lines just don’t reflect the tumors enough. What makes mini versions of organs -- or technically, 3D cultures called organoids -- different from cells in a petri dish, is how they replicate important features of the original tissue: the cell types that are present, the 3D architecture, and their self-renewal properties. Scientists have already grown human intestinal and gastric (or stomach) organoids in the lab.
Now, a large international team led by Mathew Garnett of the Wellcome Trust Sanger Institute and Hubrecht Institute’s Hans Clevers have grown 22 organoids from the tumor tissue of 20 colorectal cancer patients, with the help of growth factors and a special medium, as they described in the video below. They also grew 19 normal organoids using healthy tissue from the same patients. When they sequenced the DNA isolated from the tumor organoids, they found that the cancer-causing genetic mutations in the cultures closely matched those in the tumor biopsies -- confirming that the organoids have captured the genomic features of the tumors from which they came.
"This is the first time that a collection of cancer organoids, or a living biobank, has been derived from patient tumors," Garnett says in a news release. "We believe that these organoids are an important new tool in the arsenal of cancer biologists and may ultimately improve our ability to develop more effective cancer treatments."
Then the team screened the responses of these cancerous organoids to 83 experimental and approved cancer drugs. Because of their diverse genetic profiles, the organoids showed a huge range of sensitivities to the drugs. And some of these reactions corresponded well to known associations between specific mutations and their resistance to certain drugs. Furthermore, this screening also revealed a previously unknown gene-drug association: A subset of cancer patients with RNF43 mutations would benefit from therapy to inhibit a protein called porcupine. [Via Cell Press]
Images: van de Wetering et al., Cell 2015
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