NETRF gave an Accelerator Award to Hans Clevers, MD, PhD, Hubrecht Institute, Netherlands, to develop NET organoids to expand the field’s preclinical NET research tools in 2017. An organoid is a laboratory replica of tumor cells that researchers can study to understand the nature of neuroendocrine cancer and to test new treatments. This study won the best scientific poster award at the 2019 annual meeting of the European Neuroendocrine Tumor Society (ENETS) in Barcelona.
The Clevers lab has tried to grow 44 organoids from NET tissue samples donated for research (from tumors in small intestine, lung, and pancreas). Overall about half of the samples have grown into organoids. The lung samples have a 100% success rate. But only about one in three pancreas tissue samples successfully produce an organoid.
Dr. Clevers’ lab will study organoids made from healthy and NET cells to understand how NET cells develop. He and his team will try to isolate what genomic mutations or cellular communication errors occur. If they identify what goes wrong they will then try to recreate that error using a gene-editing technique called CRISPR/Cas9. Reproducing the formation of NET cancer cells will help confirm the exact path of the disease.
Once the cancer cell development process has been mapped, researchers will look for an opportunity to interrupt this incorrect cellular cycle. They call this an actionable target. Therapies have been developed to act upon specific targets or genomic mutations, for example, by turning cell signaling on or off that is sending the incorrect instruction to create cancer cells.
Organoids can serve as an efficient way to test various therapies in the laboratory (preclinical testing) for large-scale drug testing. The technology could also be used to advance precision therapies. An individual’s tumor tissue, obtained from a biopsy, could be used to grow a person’s own organoid. Researchers could then test a therapy on the person’s organoid first to see if it works. That could help improve the safety, efficiency, and precision of care for individual NET patients.