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Promising new technique to treat cancer receives NWO grant

Biological chemist Nathaniel Martin and his team received an NWO grant to examine how blocking a specific enzyme in our body, NNMT, could be helpful in the treatment of some cancers. Trials with mice have been promising, and together with the Netherlands Cancer Institute, Martin wants to take the next step in turning the approach into a treatment available to cancer patients.

For a few decades, scientists have known that we all have an enzyme called NNMT in our bodies. It's a protein mainly present in our liver that is believed to help us get rid of toxins. But about ten years ago, an interesting observation was made: scientists saw that NNMT, called nicotinamide N-methyltransferase in full, was also helping cancer cells to survive.

That triggered the interest of Professor Biological chemistry Nathaniel Martin because the discovery suggested that certain cancers associated with high levels of NNMT could be treated with small molecule 'inhibitors' capable of blocking that very NNMT.

Creation of a Leiden spin-out company

Now, ten years later, Martin received an NWO grant from the Open Technology Programme to continue his research. Big steps have been made since. Together with Matthijs van Haren, a former PhD researcher at Martin’s group, he recently founded a spin-out company called Cantoni Therapeutics with support from Leiden University Holdings (LEH). The aim of Cantoni is to further develop NNMT inhibitors and bring them closer to the clinic with the ultimate goal of treating patients.

That will probably take another ten years or so, Martin predicts. First, with the NWO funding, he wants to more broadly demonstrate and understand how NNMT inhibitors work to combat cancer.

The NNMT-enzym

Current evidence suggests that NNMT promotes the growth of cancer by producing a substance that is protective of cancer cells. In this regard, NNMT inhibitors such as those developed by Martin may help our body's own defense mechanisms in its fight against cancer.

Trials with mice show it’s a generally safe approach

Targeting NNMT with inhibitors has generated encouraging results. Martin and his team have successfully inhibited the enzyme in test tubes and also in mice. The good news is: 'inhibiting the enzyme doesn't appear to negatively affect healthy animals,' Martin says, making him confident that it is a generally safe approach.

Other researchers have even gone one step further and completely knocked out the gene that is responsible for the NNMT enzyme. 'Even that doesn't seem to pose any problems for the mice,' Martin says. It could mean the evolution made the enzyme superfluous. In other words: the positive effects of the enzyme are long gone, but it does contribute to the development of some cancers. However, that's an assumption that still needs to be proven.

Welcome addition to existing cancer therapies

Based on what we currently do know, Martin is optimistic that the NNMT inhibitors can be a valuable addition to existing cancer therapies. Together with the Netherlands Cancer Institute (NKI), and specifically Dr. Julia Houthuijzen, he is studying the effect of NNMT inhibitors in advanced animal models of cancer.

The NWO grant covers a period of six years and allows Martin and his group to hire two PhD students and a postdoc. Evendough researchers at other universities and pharmaceutical companies are also starting to pursue NNMT inhibitors, Martin is confident Leiden still has the edge, thanks to its pioneering work of the past few years. Human trials are not part of this NWO project, but maybe, towards the end of this decade, doctors can expect NNMT inhibitors to be available as a new tool for the treatment of cancer.

Text: Samuel Hanegreefs

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