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The Desmoid Tumor Research Foundation

January 2018

A Metabolomics Pilot Study on Desmoid Tumors and Novel Drug Candidates

Author Information

Mercier KA(1), Al-Jazrawe M(2)(3), Poon R(2), Acuff Z(4), Alman B(5)(6)

(1)RTI International, Research Triangle Park, Durham, NC, 27709, USA.(2)Developmental & Stem Cell Biology Program, Hospital for Sick Children, Toronto, ON, Canada.(3)Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada.(4)RTI International, Research Triangle Park, Durham, NC, 27709, USA.(5)Developmental & Stem Cell Biology Program, Hospital for Sick Children, Toronto, ON, Canada.(6)Department of Orthopaedics, Duke University, Durham, NC, 27704, USA.

Publication

Sci Rep

Summary

Using broad spectrum metabolomics, differences were investigated between paired normal fibroblast and desmoid tumor cells from affected patients. There were differences identified, also, in the metabolomics profiles associated with the two beta-catenin mutations, T41A and S45F. Ongoing drug screening has identified currently available compounds which inhibited desmoid tumor cellular growth by more than 50% but did not affect normal fibroblast proliferation. Two drugs were investigated in this study, and Dasatinib and FAK Inhibitor 14 treatments resulted in unique metabolomics profiles for the normal fibroblast and desmoid tumor cells, in addition to the T41A and S45F. The biochemical pathways that differentiated the cell lines were aminoacyl-tRNA biosynthesis in mitochondria and cytoplasm and signal transduction amino acid-dependent mTORC1 activation. This study provides preliminary understanding of the metabolic differences of paired normal and desmoid tumors cells, their response to desmoid tumor therapeutics, and new pathways to target for therapy.

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