22 February 2007

Dundee mathematicians aid anti-cancer drug development

(Attached picture shows Dr Robert Jackson (Cyclacel) with the Dundee University team (l-r, Hitesh Mistry (seated), Fordyce Davidson and Mark Chaplain)

The development of a new breed of "targeted" anti-cancer drugs is being boosted by mathematicians at the University of Dundee.

Dr Fordyce Davidson and Professor Mark Chaplain, both of the Division of Mathematics at the University of Dundee, have been awarded £160,000 to work with biotechnology company Cyclacel Pharmaceuticals, Inc. to develop the effective use of new anti-cancer drugs.

The grant from the Engineering and Physical Sciences Research Council will see the maths experts working 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 a new breed of "targeted" anti-cancer drugs which are specifically designed to selectively kill cancer cells, leaving most other cells in the body unharmed.

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, as 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, CYC116, an orally-available Aurora kinase and VEGFR2 inhibitor, 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."

The project is being funded by the EPSRC via the `Mathematics for Business’ scheme.

NOTES TO EDITORS

About Cyclacel
Cyclacel is a development-stage biopharmaceutical company dedicated to the discovery, development and commercialization of novel, mechanism-targeted drugs to treat human cancers and other serious disorders. The Company is currently evaluating seliciclib (CYC202), an orally-available cyclin dependent kinase inhibitor, in Phase IIb clinical trials for the treatment of lung cancer. Sapacitabine (CYC682) is an orally-available, cell cycle modulating nucleoside analog is in Phase I clinical trials for the treatment of cancer. An IND was submitted in December 2006 for CYC116, an orally-available, Aurora kinase and VEGFR2 inhibitor. Several additional programs are at an earlier stage.

Note: The Cyclacel logo and Cyclacel® are trademarks of Cyclacel Pharmaceuticals, Inc.

Mathematical Biology at the University of Dundee
Mathematical biology is increasingly influential in determining the behaviour of cells in diseases such as cancer. The University of Dundee has played a pioneering role in the development of mathematical biology. Professor James D. Murray, widely acknowledged as the father of mathematical biology, did his PhD in Dundee and Professor Mark Chaplain developed the mathematical modelling of cancer tumours in the city.

In December last year Dr Sandy Anderson published a paper detailing hiswork on developing a tumour prediction model, part of a $15million collaboration with scientists at Vanderbilt University in the USA.

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