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New drug combination could improve cancer treatments

Tuesday 10 March 2020

Associate Professor Fiona Simpson and her research team have identified a promising new drug combination that could significantly help the immune system target cancer cells and kill them.

The treatment involves a combination of an intravenous dosage of a well-known anti-nausea drug, prochlorperazine (called Stemetil in Australia), with existing cancer treatments. The study was published in leading scientific journal, Cell on Thursday 5 March, and is the culmination of over 10 years of research for A/Prof Simpson, who says the research could lead to new treatments for some cancers.

"The anti-nausea drug works by changing the surface of the tumour cells so that existing cancer drugs which target tumours are better able to interact with the immune system," Dr Simpson said.

"The result is that cancer cells become sitting targets that can no longer escape the immune system.

"We observed a process we haven't seen before and which increased the 'natural killer' immune cells' ability to attach to, and kill the cancer. It is almost as if the killer cells become zipped to the tumour cells."

The treatment can be combined with and improve the effectiveness of existing cancer drugs like cetuximab, trastuzumab and avelumab and was studied on tumours from head and neck, breast and metastatic colorectal cancers in mice, as well as five patients with head and neck cancer.

"These heroic patients volunteered for a 'no benefit trial', consenting to have a tumour biopsy followed by a 20-minute intravenous transfusion of Stemetil, and then another biopsy," Dr Simpson said.

"We were able to show that the Stemetil altered the tumour cell surface in these patients."

Following the initial findings, the researchers combined Stemetil with an anti-cancer antibody drug resulting in the disappearance of all the tumours from ten mice with head and neck cancer. Dr Simpson then re-introduced the same cancer back into the mice four weeks later.

"Amazingly, their cancer was rapidly eliminated - as if the new combination, in addition to being more effective, was also able to teach the immune system how to better recognise cancer cells," Dr Simpson said.

"The mice developed a long-term immunity to the cancer they initially had."

The research group have been working with expert immunologists including UQ's Dr James Wells to translate the findings to patient treatments.

"Our long-term vision is to use this approach to not only clear a patient's cancer in the immediate term, but to prevent their cancer coming back in the future by establishing protective 'immune memory'," Dr Wells said.

A/Prof Simpson and her team are now completing a safety trial of the combination of drugs in head and neck cancer, triple-negative breast cancer and adenoid cystic carcinoma patients at the PA Hospital. The PA Research Foundation have been able to help progress A/Prof Simpson's research project and the safety trial thanks to the generous support of donors and partners.

The team requires additional support to progress their work to Phase II trials which will involve a larger patient cohort across multiple sites. To support this important research, donate here.

Adapted from an article originally published by UQ here.