New therapy breaks down fibrotic barrier around solid tumours

Tuesday, 26 Nov 2019

Australian researchers have developed a therapy that breaks down the fibrous barrier surrounding solid tumours and enhances delivery of anti-cancer drugs to tumour cells.

Perth scientists have shown that the extracellular matrix (ECM) targeting peptide, CSG, can be used as a ligand to target TNFα into the thick scaffold of collagen glycoproteins and glycosaminoglycans that form an obstructive physical barrier to  cells and therapeutic compounds entering a tumour.

In their study they showed that delivering the cytokine into the fibrous tissue stimulated proteases that reduced tumour stiffness, promoted decompression of tumour blood vessels, and enhanced tumour perfusion.

In mouse and human tissue models they showed that the TNFα‐CSG treatment had the potential to improve drug delivery and also to suppresses tumour growth, suggesting activation of adaptive tumour immunity, but without systemic toxicity due to its high selectivity for the ECM.

“The barrier around some cancers, such as liver cancer, pancreatic cancer and some breast cancers is like barbed wire,” said Dr Juliana Hamzah, head of the Targeted Drug Delivery, Imaging and Therapy Laboratory at the Harry Perkins Institute of Medical Research, Perth.

“It is stiff, non-cellular, has very few blood vessels and impenetrable. The scar tissue is not only a physical barrier but it constricts blood vessels which are key pathways for delivering cancer treatment,

“We have developed a non-toxic agent that does not affect surrounding healthy tissue.

“The agent activates immune cells to release enzymes that digest the scar tissue. This allows more cancer killing immune cells to enter the tumour. Our results show that removal of the fibrous tissue dramatically eliminates the drug delivery barrier.

“Tumours treated with the drug we’ve developed are more permeable to anti-tumour immune cells and cancer treatments”, Dr Hamzah said.

And now that the drug has been proven to have a positive impact on fibrosis, she is investigating whether it can be used to prevent malignant cancer by treating the early stages of fibrosis in liver cancer.

“If you take liver cancer, it doesn’t start immediately as cancer, it starts as fibrosis, cirrhosis, which then develops into liver cancer.

“Because chronic tissue fibrosis can lead to cancer we aim to investigate whether early treatment with our drug of the pre-cancerous stage, such as liver fibrosis, could prevent development of malignant cancer.

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