Sulindac (Merck): a non-steroidal anti-inflammatoryĮrlotinib (Astellas Pharma U.S.): a tyrosine kinase inhibitor that slows the growth of cancer cells with specific proteins (“EGFR”) on their cell surface. Additional clinical trials involve the repurposing of icosapent ethyl used to prevent heart attacks (GLW Pharma), sirolimus (Emtora Biosciences), used after renal transplants to prevent rejection of the new kidney and the drugs chosen for the study below. Janssen Pharmaceuticals (part of Johnson and Johnson) are performing clinical trials using this drug to treat FAP patients. It works by blocking inflammatory and immune responses. Since safety in humans has already been demonstrated, the drug development timeline and the research and development costs are significantly reduced.Īn example of this is a drug called guselkumab (Tremfya), that is used in the treatment of plaque psoriasis. Work is ongoing to find novel treatments and to explore the use of existing drugs that have already been approved for clinical use. To date, no suitable drugs have been discovered that fulfil these needs. This would prevent, or at least delay the growth of polyps and therefore disease progression and cause no unwanted side-effects. The ideal treatment for FAP and MAP patients would be to correct or neutralise the effects of the faulty instructions in these patients. The organoids (“mini-guts”) are spheroidal in shape with a hollow interior (equivalent to the lumen of the intestine). ![]() The red stain is a marker for cytokeratin, a protein which is specifically found in the lining of the stomach and intestine. The blue stain identifies DNA in individual cells. Duodenal adenoma and normal 3D organoid lines from the same patients (for comparison), were successfully derived and expanded.ĭuodenal adenoma organoids derived from biopsy tissue from a FAP patientĬompressed 3D image projection of a duodenal adenoma FAP organoid taken using a Zeiss 880 LSM microscope by the ITSR group at Cardiff University. The project succeeded in obtaining living duodenal tissues donated by affected patients. They are used as models for research into the causes and effects of the diseases and as a platform for pre-clinical testing of preventative treatments. Organoids derived from intestinal biopsy material from FAP and MAP patients, replicate the biology and appearance of duodenal adenomas or of normal tissue, depending on where the biopsy was taken from. Organoids are 3D cell structures that are miniaturised versions of the tissue from which they originated. In a joint project with Cellesce, these models have been developed further, for use in an industrial environment, to facilitate drug discovery. The Inherited Tumour Syndromes Research (ITSR) group at Cardiff University has been developing 3D organoid cell models to represent duodenal malignancy in FAP and MAP patients. The gastro-intestinal tract (image from University of Missouri Health Care) Research into this area is a high priority as there are high economic and quality of life costs associated with both diseases. ![]() Very little is known about the causes of duodenal polyps and how this differs from colorectal disease in FAP and MAP. Further surgery may be required if polyps form in the duodenum (duodenectomy). Endoscopy involves the insertion of a long, thin, flexible tube that has a tiny video camera at the end so that clinicians can closely observe the lining of the intestine as the tube is fed through. Treatment is by preventative colectomy (removal of some, or all the colon) and regular endoscopic examination of the upper intestines. The diagnosis is made by analysing the genetic code of the patients to look for specific mutations in the DNA that indicate why the instructions for normal cell growth have been corrupted. ![]() MAP may be less severe than FAP with fewer polyps developing and later. The average age for polyps to develop in patients with FAP is the mid-teens, with multiple polyps developing by the age of 35. Colorectal cancer progression (image from Guts UK Charity)
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