Forðing av Phosphodiesterase 8A enzym fyri at minka um varandi bruna og krabbakyknusperiðing.
Nicolina Maria Ovadóttir
Verkætlan á Deildini fyri heilsu- og sjúkrarøktarvísindi á Fróðskaparsetrinum
Amanda Vang og Jesper Troelsen
Stuðul úr Granskingargrunninum:
Summary of project. Please note that if application is granted, the summary will be published on the Research Council’s website. (Complete description of the project is required and must be enclosed separately, max 10 pages –please consult Formal Requirements and Guidelines for applications) Resistance to chemotherapeutic drugs presents a significant challenge in treating Colorectal Cancer (CRC). Therefore, alternative effective therapies targeting both the inflammation signals driving tissue destruction and the migration of cancer cells are needed. Phosphodieseterase 8A (PDE8A) stands at the crossroads of chronic inflammation and migration with the potential to be a key therapeutic target to treat both the inflammation driving the early stages of CRC development from Inflammatory Bowel Disease (IBD) and the migration of cells during progression of CRC. IBD is an umbrella term mainly used to describe two conditions: Ulcerative Colitis (UC) and Crohn's disease. IBD is a significant risk factor for CRC and is linked to an excessive and abnormal immune response in the gut. Chronically active IBD contributes to the development of low- and high-grade dysplasia, which increases the risk of CRC development. At 74 per 100.000, the incidence of IBD on The Faroe Islands is more than double of what is seen in the rest of Europe. The goal of this project is therefore to determine the inhibitory effect of selective PDE8A inhibition to reduce chronic inflammation and cancer cell migration. Taken together with our collaboration involving the effect of PDE8A inhibition on gene expression in CRC cell lines and our in situ data on PDE8A localization in UC and CRC, this data will contribute to the rationale for clinical trial testing of PDE8A inhibitors in chronic IBD patients at high risk for developing CRC and to provide an alternative therapy for IBD and chemo resistant CRC.