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Anglia Ruskin University study shows drug targeting annexin-A1 can halt cancer cell growth





The effectiveness of the first therapeutic drug to target annexin-A1 - a protein overexpressed in several cancer types that promotes the progression of tumour - has been demonstrated in a new study involving Anglia Ruskin University researchers.

High annexin-A1 expression levels are associated with poorer survival rates for patients with various cancers that so far have limited treatment options, including triple-negative breast, pancreatic, colorectal and prostate cancers.

A cancer scan
A cancer scan

MDX-124, a monoclonal antibody therapy being developed for use in immunotherapy by Scottish biotech company Medannex, has now been shown to reduce proliferation significantly in a number of human cancer cell lines expressing annexin-A1, by stopping the cell cycle progression.

MDX-124 has also been shown to inhibit tumour growth significantly, using in vivo models of triple-negative breast and pancreatic cancer.

The study was led by Prof Chris Parris and Dr Hussein Al-Ali at ARU in collaboration with Prof Chris Pepper, of Brighton and Sussex Medical School, along with the company, and suggests annexin-A1-targeted therapy represents a viable and innovative approach to cancer treatment. The findings were published in Oncogene, Nature’s cancer journal, and a phase Ib clinical study of MDX-124, called ATTAINMENT, is now under way to establish the safety and optimum dose of the novel therapy.

Its clinical efficacy will be evaluated in newly-diagnosed cancer patients, in combination with current appropriate treatments.

Prof Parris, head of ARU’s School of Life Sciences, said: “We know that the protein annexin-A1 activates formyl peptide receptors to initiate a complex network of intracellular signalling pathways, which can lead to numerous cellular responses, including tumour initiation and progression.

“We have demonstrated in this new study that using MDX-124 can reduce cell growth in annexin-A1-expressing cancer cells both in vitro and in vivo, providing further evidence that annexin-A1 is a valid target for therapy in cancer.”

Medannex director of scientific operations, Dr Fiona Dempsey, who co-authored the paper, said: “We are delighted to publish this work with our collaborators demonstrating the anti-cancer potential of our innovative antibody therapeutic and look forward to the clinical data coming out of the ATTAINMENT study in due course.”

Read the paper at https://www.nature.com/articles/s41388-023-02919-9 and visit https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-mdx-124-for-solid-tumours-that-have-spread-attainment for more on the ATTAINMENT clinical study.



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