In a paper published in the journal Biomolecules, UK and Chinese researchers report their creation of a biomedical compound that has the potential to stop breast cancer metastasis.
The scientists from the Chemistry and Biochemistry Departments at the University of Liverpool and Nanjing Medical School in China have discovered a possible way to block proteins produced by cancer cells that promote metastasis – the chief impediment to successful cancer treatment.
Prof Philip Rudland from the University of Liverpool explained: “As a general rule, cancer that has spread is treated with chemotherapy, but this treatment can rarely be given without severely harming or becoming toxic to the patient. The importance of our work was to identify a specific and important target to attack, without toxic side effects.”
The University’s research team have in the past discovered that specific proteins are involved in the metastatic process; these proteins are different from those involved in the production of the primary tumour. One such example is a protein called ‘S100A4’, and is the protein chosen by the research team to target for the identification of chemical inhibitors of metastasis, using model systems of cells from the highly metastatic and incurable hormone receptor-free breast cancer.
Using these model systems, researchers at the University’s Department of Biochemistry discovered a novel compound that can specifically block the interaction of this metastasis-inducing protein S100A4 with its target inside the cell. Researchers in the Department of Chemistry then synthesised a simpler chemical and connected it to a warhead which stimulates cells’ normal protein-degrading machinery. This compound now works at very low doses to inhibit properties associated with metastasis, an improvement of over 20 000-fold on the original unarmed inhibitor, with virtually no toxic side effects. Moreover, in collaboration with Chinese researchers at Nanjing Medical School, they have shown that this compound inhibits metastasis in similar metastatic tumours in mice, suggesting a potential therapeutic role.
Dr Gemma Nixon, Senior Lecturer in Medicinal Chemistry at the University of Liverpool said: “This is an exciting breakthrough in our research. We now hope to take the next steps, and repeat this study in a large group of animals with similar metastatic cancers so that the efficacy and stability of the compounds can be thoroughly investigated and if necessary improved by further design and syntheses, prior to any clinical trials.”
“Significantly, this particular protein we’re investigating occurs in many different cancers, which could mean this approach may be valid for many other commonly occurring human cancers.”
Source: University of Liverpool
