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Gamma secretase inhibitors and desmoid fibromatosis Lessons from a real world, comprehensive genomic study

Background

  • Recently, first-in-class FDA approval was granted in the U.S. for use of the gamma secretase inhibitor (GSI), nirogacestat, for adults with progressive desmoid fibromatosis (DES)1.
  • The unpredictable clinical behavior of desmoids, which ranges from local aggression to regression2, raises consideration of whether diagnostic and molecular variability underlie their varying biological potential. 
  • With an aim to understand both, and to explore the potential for biomarkers for GSI therapy selection, prediction, and prognosis, we performed a retrospective review of comprehensive genomic profiling and histology of desmoids and other soft tissue tumors (STT) harboring CTNNB1 or APC mutations.
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