Normally we use chemotherapy and radiotherapy to treat cancer and this is causing DNA damage. We’ve come up with an enzyme that actually is a non-essential enzyme for normal cells but that is absolutely required to take care of the DNA damage already present in the cancers, so this is the damage occurring to the building blocks of DNA. The building blocks are damaged a million per cent more often than the DNA itself. This enzyme, MTH1, this MTH1 enzyme is involved in removing and preventing, sanitising these oxidised nucleotides to be incorporated into the DNA.

This is absolutely essential for cancer cells. If we remove this enzyme cancer cells die, all cancer cells, it doesn’t matter what the genotype is. So any cancer dies but the interesting thing is that this is not needed for normal cells. Normal cells have regulated redox pathways; we have cells that live for a hundred years, we don’t need this enzyme. So cancer cells absolutely need it, normal cells do not.

We’ve been developing inhibitors for this MTH1 protein and these inhibitors effectively kill off cancer cells, they introduce damage into the DNA in cancer cells but not to normal cells. So they are very highly toxic to cancer cells and we can see even the most resistant, multi-resistant tumours go away. These small molecules go into the MTH1 and these are orally available so these will be pills. So they go into the enzyme, the pocket of the enzyme, and then inhibit it and then you get incorporation of the damage. You produce chemotherapeutic kind of damage with these small molecule inhibitors in all cancer cells by just inhibiting this enzyme and not in the normal cells. So we have very specific selective toxicities with the cancer cells.

Now, admittedly this is at an early stage. So we have produced these inhibitors, we have them pharmacologically safe and so forth but we need of course to test them in clinical trials. This is where we reach out to clinicians across the globe to help us. We are providing molecules but we also need help to see how can we introduce these in all different types of cancers. Because I think we need to carve out and understand how are we going to introduce it in each specific cancer. To our understanding it works for all cancers we’ve tried on but we need to have it really working out for all the different types of cancers. That’s where you may have, as a clinician, a specific cancer that you’re interested in that you could email us, we’ll send you the inhibitors and we’ll set up a trial together and we’ll see how it works.

Can you screen people for this particular enzyme to see who might be a good candidate?

So far we don’t have really that much information which cell lines are more sensitive or less sensitive to this inhibitor. We’ve found that they’re all sensitive. The level is expressed, so this enzyme is not expressed in normal tissue but it’s highly expressed in cancer. So obviously what we can do is that we can look at the levels of the MTH1 protein but, to our understanding, it is not really determining the efficiency of the therapy. Of course, we need to work out more biomarkers but this is also targeting the cancer phenotype. It is not targeting the cancer genetics; this is not the personalised cancer therapy approach. It works like taxols or cisplatin for many different cancers. So it’s not that we need to tailor this for the individual patients; these are orally available pills that can be given to many different patients.

Were there radiosensitising properties?

This drug could potentially be radiosensitising because most of the damage caused by radiation is actually caused to the free bases, not the DNA itself, so therefore it could be important. However, when we do this in the test-tube we typically expose to high doses of ionising radiation causing double strand breaks. But, in the clinical setting we give low doses of sub-lethal doses which actually are more important. So I think this is more important to understand how it works in the clinic rather than understanding how it works in vitro. We do know that after extremely low doses of ionising radiation such as 5mGy this enzyme is the first enzyme to be upregulated, MTH1. So even at 5mGy it is upregulated so we do think that it is very important for radiation damage. But then, of course, how we’re exactly going to carve out and implement this into the clinic, we need your help. We need the help of all the clinicians to see how we can do this.