Drugs That Regulate Heparan Sulfate Expression for Cancer Treatment

Tech ID: 23T141

­Advantages:

  •  Developed a novel assay for identifying repurposed drugs targeting HS-related gene expression
  • Revealed a  dose-dependent inhibition of the HS-related gene EXT1 with Vitamin D/ Calcitriol
  •  EXT1 stable cell line with luciferase reporter ensures specificity in identifying EXT1 regulators, minimizing off-target effects

Summary:

Heparan Sulfate (HS), a linear, sulfated polysaccharide, plays pivotal roles in fundamental cellular activities such as adhesion, migration, proliferation, and differentiation, influencing various physiological functions. However, aberrations in HS expression are associated with various pathological conditions, including cancer, inflammation, and developmental disorders.

Our investigators developed a  high throughput screening (HTS) to identify drugs capable of modulating HS-related gene expression. Using a stable cell line with promoter luciferase reporter of the HS-biosynthetic gene EXT1, the EXT1 and other HS-biosynthetic gene reporter cell lines were screened with an FDA-approved drug library. This research discovered that decreased HS gene expression, EXT1 gene expression, was achieved with vitamin D or its analogs (e.g. calcitriol). These inhibitors can potentially be administered in combination with a cancer therapy.

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Vitamin D3 Dose Response Curve

 

Desired Partnerships:

  • License
  • Sponsored Research
  • Co-Development

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