Protein blockers could stop cancer spread

Scientists from the University of Liverpool and Southeast University Medical School have discovered a possible way to block proteins produced in the body when a patient has cancer, which cause the cancer to spread to other parts of the body. This process, called metastasis, is the major problem hindering the successful treatment of commonly occurring cancers.

“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,” said Professor Philip Rudland from the University of Liverpool. “The importance of our work was to identify a specific and important target to attack, without toxic side effects.”

Liverpool researchers 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’, which was chosen by the research team 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 the 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 the normal protein degrading machinery of a cell. 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.

In collaboration with researchers at Southeast University Medical School, the team showed that this compound inhibits metastasis in similar metastatic tumours in mice, suggesting a potential therapeutic role. Their results have been published in the journal Biomolecules.

“This is an exciting breakthrough in our research,” said Dr Gemma Nixon from the University of Liverpool. “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.”

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