1 December 2006

Tumour "weather forecast" gives new insights in cancer

The aggressiveness of cancer tumours may be determined by the tissue environment in which they grow, new research from the University of Dundee shows.

Dr Sandy Anderson, of the Division of Mathematics at Dundee, has developed a mathematical model - similar in concept to weather forecasting but considerably more complex - which predicts how tumours grow and invade tissue. The results produced by the model have given startling insights into how cancerous tumours develop in the body.

"What this model predicts is that the more barren and harsh the tissue environment surrounding it is, the more aggressive the tumour becomes," said Dr Anderson.

The findings have the potential to impact on how certain cancers are treated, by forcing the environment around the tumour to be considered as a contributory factor in how aggressive the cancer is.

The combination of maths and laboratory research to develop such models has been hailed as a "new era in cancer research" by Professor Vito Quaranta, a leading American cancer biologist who is collaborating on the project.

Professor Quaranta envisions a future when computer simulations like this will be used to predict a tumour’s clinical progression and formulate treatment plans, in a fashion not dissimilar to how we forecast the weather now.

"Today we can know pretty well that for the next few days we’re going to expect good weather or that there’s a storm on the way," said Professor Quaranta. "That’s the kind of predictive power we want to generate with our model for cancer invasion."

Dr Anderson’s research is published in the scientific journal Cell today, December 1st 2006, and is one of the few purely mathematical modelling papers to appear in the history of this prestigious biological journal.

"What our research shows is that the micro-environment in which the tumour grows acts like a Darwinian selective force upon how the tumour evolves," said Dr Anderson.

"Much of current biomedical research being carried out on cancer is done in isolation of the real environment in which the tumour naturally grows, but these results show that this environment could be the crucial determining factor in the tumour's development."

The model developed by Dr Anderson also shows a clear relationship between the shape of a cancer tumour and how aggressive it is. Aggressive tumours tend to assume a spidery shape in the model, while more benign growths are generally more spherical in shape.

"This is important in terms of the surgical removal of tumours," said Dr Anderson. "A model like this could help predict how tumours will grow in different tissue environments, i.e. different areas of the body, and what the best strategy may be to treat them."

"One interesting aspect of this is that if you make the environment the tumour is growing in more harsh or barren, then the more likely it is that any surviving cancer cells will be the most aggressive and hardiest ones."

"This clearly has a potential to impact on how certain cancers are treated, since most of the current treatment strategies are focussed on making the tissue environment as harsh as possible for the tumour in the hope of destroying it. But as my research predicts this could allow the most aggressive cancer cells to dominate any residual tumour left after treatment and since these more aggressive cells tend to be the most invasive, this could result in an increased chance of metastasis."

"In the future this research could help tailor treatment in a patient specific manner, with the mathematical model being an additional weapon in the armoury against cancer."

Dr Anderson is collaborating on his work with experts in cancer biology at Vanderbilt University in the United States, led by Professor Vito Quaranta and Dr. Alissa Weaver in conjunction with Professor Peter Cummings (Chemical Engineering), who are in the process of carrying out the physical validation of the results produced by the mathematical model.

Professor Quaranta hailed the combination of mathematics and laboratory research as a major development in how we approach cancer.

"A new era in cancer research has begun," said Professor Quaranta. "Mathematicians are bringing entirely new vistas to our field, cancer is no longer an ugly beast to defeat, but rather it is a complex process that can be described rationally and conquered perhaps slowly, but surely."

"I have never been more optimistic about our prospects of understanding the inner workings of cancer progression, to the same level we understand other complex processes, such as weather formation, global warming, etc."

"Understanding the individual components of cancer progression is still a necessary task, but it is no longer sufficient: It is how the components interact with each other that determines outcome. Our work shows this clearly, the genetic changes in cancer cells interact dynamically with their immediate surroundings, with outcomes that remind us of the natural selection process in evolution."

"The long-term goal is that, with the tools of mathematical modeling and computer simulation, cancer treatment will no longer be a trial and error guessing game. With mathematics-driven oncology research, we will be able to determine which drugs will work at which stage."

The project has been funded by $15 million from the National Cancer Institute and the National Institute of Health in the USA.

NOTES TO EDITORS

A photograph of Dr Anderson and Professor Quaranta is available from the University of Dundee Press Office. Diagrams of the growth of a cancer tumour and a schematic diagram of how the model works are also available.

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.

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