Novel method for enhancing tumours’ response to treatment

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A team of researchers have innovated a new strategy that increases tumour receptiveness to cancer drugs, potentially augmenting the effectiveness of chemotherapy treatments.

The research, led by Massachusetts General Hospital (MGH), indicates that their new strategy enables tumours to respond to cancer drugs more effectively, showing promising signs for the development of chemotherapy treatments. Their study is published in Nature Nanotechnology.

One of the most significant roadblocks that obstruct effective cancer therapy is supplying tumours with sufficient anticancer drugs. The new strategy to achieve this involves binding the medications to albumin – the most abundant protein in the blood, relying on satiating the tumours appetite for protein nutrients that inhibit malignant growth. Therefore, while the tumour is consuming the albumin, they will involuntarily be taking the attached drugs.

Utilising nab-PTX

A popular albumin-bound drug that has been utilised in the treatment of late-stage lung and pancreatic cancer is nanoparticle albumin-bound paclitaxel (nab-PTX), a drug approved by the U.S. Food and Drug Administration.

Miles Miller, the senior author of the study and principal investigator at the MGH Center for Systems Biology, said: “Not all patients respond to nab-PTX, though, and the effectiveness of its delivery to tumours has been mixed, owing to an incomplete understanding of how albumin impacts drug delivery and actions.”

To investigate their hypothesis, the team analysed the implementation of nab-PTX to tumours at a single-cell resolution in mouse models of cancer, employing 3D microscopy and tissue clearing technology. From their analysis, the team discovered that cancer cells could intake a substantial amount of nab-PTX, with the ingesting of the drugs manipulated by signalling pathways that are vital in the cells’ absorption of nutrients such as albumin.

Ran Li, the first author of the study and an instructor in the MGH Department of Radiology and the Center for Systems Biology, said: “This discovery suggested that if we could manipulate these pathways, we might be able to trick cancer cells into a nutrient-starved state, thereby enhancing their consumption of nab-PTX.”

By administering an inhibitor of insulin-like growth factor 1 receptor to the tumours, the accumulation of nab-PTX in the tumours was considerably improved. “These results offer new possibilities to improve the delivery of albumin-bound drugs in patients with diverse types of cancer,” said Miller.

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