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Targeting breast cancer metastasis with heparan sulfate mimetics

Year:
2018
Duration:
29 months
Approved budget:
$100,000.35
Researchers:
Professor John Miller
Health issue:
Cancer (oncology)
Proposal type:
Joint Research Partnership Project
Lay summary
Human breast cancer cells express heparanase, an enzyme that degrades the extracellular matrix that surrounds cells, including tumour cells. This breakdown of the matrix facilitates escape of the tumour cells and entry into the circulation, leading to the formation of secondary tumours (metastasis), the main cause of cancer death. Heparanase is therefore a highly druggable target for breast cancer therapy. Our approach will be to prevent the action of heparanase on the extracellular matrix with non-toxic heparan sulfate-based compounds. Currently, there are no therapeutically effective heparanase inhibitors available in the clinic. Preliminary animal trials have shown our heparan sulfate compounds have low toxicity and significantly retard the spread of cancer cells. Our research will combine leading expertise in synthetic and medicinal chemistry and cancer biology to evaluate our compounds in triple-negative, metastatic human breast cancer cell lines in culture and in animal models of breast cancer.