A PhD student from the University of Bradford has made a promising new discovery involving the use of tumour-targeted methotrexate to treat osteosarcoma.

Hannah Spencer was funded by a PhD Studentship awarded to Professor Rob Falconer at the University of Bradford. Together with other members of Professor Falconer's research team and collaborators at the University of Sheffield and University of Manchester, they were able to create chemically modified methotrexate that can be activated within a tumour and not absorbed by the rest of the body.

It is hoped that this will result in reduced toxicity when methotrexate is used to treat osteosarcoma patients.

The current chemotherapy combination given to patients before and after surgery, known as MAP, is made up of high-dose methotrexate, doxorubicin, and cisplatin. High-dose methotrexate is used to ensure that enough of the drug reaches the tumour site.

Because the drug cannot differentiate between cancerous and normal cells, it results in very severe toxicity. As a consequence, its dose often needs to be reduced and occasionally abandoned altogether, which has a negative impact on patient outcomes.

Matrix metalloproteinases (MMPs) are enzymes whose role is to split amino acid chains that form proteins. They are found in high volumes in osteosarcoma tumour cells.

Professor Falconer and his team were able to "hide" methotrexate among a number of amino acid chains that were broken down by these enzymes, allowing the drug to be "freed" only at its intended destination. This means that it is inactive when administered into the bloodstream and becomes active only at the tumour site, thereby reducing the toxic effect it has on healthy cells.

This could result in a dramatic reduction in side effects compared to the methotrexate that is currently administered to osteosarcoma patients.

The Bone Cancer Trust has recently awarded funding for the next four years to enable the continuation of this research. Future studies will further explore the optimisation of methotrexate to treat osteosarcoma in advanced laboratory models.

Find out more about the research project below:

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