Maths aids anti-cancer drug development

Dr Robert Jackson (Cyclacel) with the Dundee University team (l-r, Hitesh Mistry (seated), Fordyce Davidson and Mark Chaplain. (image by fotopress)

Dundee mathematicians are to play a key role in the design of a new breed of clever anti-cancer drugs that selectively kill cancer cells while leaving other cells in the body unharmed.

Dr Fordyce Davidson and Professor Mark Chaplain in the Division of Mathematics will work alongside Cyclacel's Chief Scientific Officer, Dr Robert Jackson, and scientists at Cyclacel's Dundee, Scotland, laboratories on the company's new drug candidate, CYC116, one of their "targeted" anti-cancer drugs, to find the most effective way of using the new medication.

The University team were awarded £160,000 by the Engineering and Physical Sciences Research Council under their 'Mathematics for Business' scheme to work on the project.

One of the big challenges faced by doctors when treating cancer is to find out quickly whether a given treatment is effective or not for a particular patient. For certain cancers it can be very difficult to measure how quickly the tumour is shrinking in response to treatment - or indeed if it is shrinking at all. It can take several weeks before any change becomes apparent on a scan, for example. For particularly aggressive cancers, this delay can be lethal for the patient.

One possible way around this is to find other methods of measuring whether cancer cells are dying as a result of the treatment. The Maths Department at the University of Dundee has in recent years developed pioneering techniques in mathematical biology, using modelling to map the development of cancer tumours.

When cells are killed by anti-cancer drugs, tell-tale biochemical markers are released into the blood stream by the cell and it is possible that these 'biomarkers' could be used as a quick and accurate measure of the effectiveness of a drug. The test could be as simple as taking a blood sample.

However, Dr Davidson explains, "The relationship between the amount of anti-cancer drug given to the patient, the effect that drug has on tumour cells and the subsequent concentration of biomarkers in the blood stream is very complex."

"Unfortunately it is not simply the case that higher quantities of a drug kill more cancer cells, it can be unpredictable. Moreover, all drugs can be harmful in large doses, so treatment has to be a clever balancing act."

"It is here that as mathematicians we will help by using powerful tools of mathematical modelling and analysis to understand the processes that take place once the drug is administered and how it can be most effectively applied."

The Dundee mathematicians, including new recruit Hitesh Mistry, will work closely with Cyclacel's scientists, to produce models of how the dose of Cyclacel's drug candidate impacts on tumour cell death and how this is reflected in the concentrations of biomarkers in the blood stream.

Dr Davidson said the advances being made in applying mathematical models to cancer diagnosis and treatment could help usher in a new era of personalised medicine.

"Ultimately this could lead to mathematical models in the form of computer packages being used by clinicians who would be able to key in information about a particular patient," he said.

"The model would then tell the clinician the most appropriate treatment regime and would also be able to help identify whether the chosen drug treatment was working. It is very exciting for us to be working with Cyclacel, developing this new technology alongside the new drug candidate".

Dr Robert Jackson, Cyclacel's Chief Scientific Officer commented, "The drug development process is becoming increasingly computer-intensive. The mathematical approaches being developed by Dundee University and those which we are using at Cyclacel together with our own biomarker analysis will help drug developers to interpret their biomarker data, and in the long term may increase drug development success rates and match patient treatments to their individual circumstances."