Desmoid tumors (DT) are locally invasive soft tissue growths with no directed therapies currently. While two genes (β-catenin and adenomatous polyposis coli) have been found in patients who develop desmoids, it is unclear how these mutations and other downstream mechanisms lead to desmoid tumorigenesis. Extensive research has been explored in the molecular biology of desmoids; however, the use of metabolomics to understand the how the low molecular weight complements of cells, tissues, and biological fluids are perturbed by this highly localized disease. Additionally, the Desmoid Collaboration for a Cure has identified 45 active drugs against primary cell lines. It is unclear how these therapies perturb the metabolome, outside the Wnt and notch pathways. This proposal will use broad spectrum metabolomics to study the tumorigenesis process of fibroblasts to desmoids by investigating paired desmoid and fibroblast cell lines, in addition to unaffected fibroblast cells. Additionally, this proposal will explore the effects of three of the active drugs identified by Collaboration for a Cure on the desmoid and fibroblast cells. It is our hope that this research project will provide knowledge to understand more about the biochemistry of desmoid formation from normal tissue, and how these drugs will help fight desmoid tumors.
LAY VERSION OF ABSTRACT- A metabolomics pilot study on desmoid tumors and novel drug candidates
