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Heparan sulfate(HS) mimetics

  • Heparan sulfate(HS) is a mixture of highly sulfated, monophosphorylated mannose oligosaccharides, derived from the extracellular phosphomannan of the yeast Pichia holstii, with potential antiangiogenic activity
  • HS mimetics inhibit heparanase (endo-beta-D-glucuronidase heparanase)
  • Increased heparanase activity has been implicated in tumor angiogenesis and metastasis
  • HS mimetics interfere with the heparanase-mediated degradation of heparan-sulfate proteoglycans in extracellular matrices, an important step in the metastatic process
  • HS mimetics bind with FGF1 and 2, thereby reducing their functional activities and inhibiting VEGF and FGF stimulation of tumor angiogenesis
  • Currently, there are several kinds of HS mimetics such as PI-88, M402, PG545, SST0001. As of 26 January 2015, all 520 patients in the PATRON trial (to evaluate effectiveness of PI-88 for adjuvant treatment of HCC after surgical resection) have completed treatment with either PI-88 or the placebo

Current status & perspective

  • Completed collection of HCC tissues from HCC patients administered with HS mimetics
  • Completed development of biomarkers to predict eligibility for HS mimetics treatment (Diagnostic performance: 77% accuracy)
  • Our biomarkers could be commercialized as CDx test for many types of HS mimetics such as PI-88, M402, PG545, SST0001