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New targets for cancer drugs

A new type of potential target for the treatment of cancer is to undergo fundamental analysis as scientists from Karolinska Institutet, Stockholm University and Uppsala University team up to examine the proteins involved in the production of the building blocks of DNA

The project is aimed at the nucleotide hydrolase protein family, which has a role in ensuring that the building blocks of DNA remain intact. The DNA components of cancer cells can be more damaged than normal cells owing to high levels of oxidative stress. The researchers' previous studies suggest that these proteins are specifically crucial to the survival of cancer cells. In this project, they will be studying the proteins and producing inhibitors in order to establish whether they can specifically kill cancer cells.

Specific inhibitors

While the structure and function of several nucleotide hydrolases are still unknown, they will now be analysed down to the smallest biochemical and biological detail. Small molecules that can inhibit the nucleotide hydrolases will be identified, specific molecules for each one. The chemical and pharmaceutical properties of the inhibitors most effective at killing cancer cells with minimal adverse effects will then be studied in more detail, after which promising candidates can be taken to clinical trial.

"Our aim in this project is to develop a fundamental understanding of a group of as-yet unknown proteins," says Professor Thomas Helleday of Karolinska Institutet, coordinator of the project. "At the same time, we already have an accepted hypothesis that this protein group will benefit cancer patients within the foreseeable future."

The project will gather a wide range of specialist researchers, including molecular biologists, chemists, structural biologists, pharmacologists and clinicians. The basic studies will be carried out at the Science for Life Laboratory in Solna. The clinical studies will initially focus on breast and haematological cancer.