Cancer: radical new approach to be proposed

A radical new approach to cancer is to be announced in London tomorrow (Wednesday 5 June), in a lecture hosted by the magazine New Scientist.

Prof. Paul Davies

Prof. Paul Davies

The speaker, Prof. Paul Davies, is a theoretical physicist whose usual research tools are pen and paper. He has been brought to the fore in cancer research as the result of an initiative by the US National Cancer Institute.

The call came in 2007 from the Institute’s deputy director, who told him that the 40-year-long ‘War on cancer’ had not made the progress that had been hoped for. 100 billion dollars had been spent, but life expectancy had hardly altered in the many cases when cancer had spread through the body. Massive amounts of data had been built up by researchers, but no new concepts were forthcoming. So, Prof. Davies was told, the biologists were calling for help from other areas of science, in a process that has since led to the establishment of twelve new research centres across the US.

‘With no prior knowledge of cancer, I started asking some very basic questions,’ he says. ‘What struck me from the outset is that something as pervasive and stubborn as cancer must be a deep part of life itself.

‘Oncologists tend to think of cancer as a motley collection of cells gone berserk, but to me the way that tumours grow and spread to other organs indicates an organised and systematic strategy, designed to evade all that the body and the medical profession thrown at it. Such well-honed behaviour suggests they are the product of a long period of biological evolution.’

Cells that work together

Dr-Charles-H.-Lineweaver

Dr Charles H. Lineweaver

Prof. Davies, who runs a research centre at Arizona State University, brought in a second physicist to explore ideas. Dr Charles Lineweaver of the Australian National University has a similar background, in cosmology and astrobiology, where the search for life elsewhere in the universe is leading to fundamental questions about its nature.

Together they worked on a new approach. Up till now, they argued, cancer has been thought of as a kind of anarchy, where rogue cells in the body break free from their normal duties and pursue an agenda of their own and improvise new strategies. But in fact, they say, what stands out is the way in which cancer cells cooperate with each other for a common benefit.

‘The most striking example of this is angiogenesis, in which an entire tumour builds its own blood supply for the common good of all the tumour cells.’

In other words, cancer cells resemble ecosystems, consisting of a diverse population – ‘rather than a collection of fiercely competitive individuals’.

Further, the strategies that cancer cells adopt are so sophisticated and coordinated that they look like the result of a built-in programme.

In particular in metastasis, when cancer spreads from a primary tumour, the activity looks very organised indeed, as cells migrate through the blood system, hooking themselves onto blood vessel walls and making their way into the nearest organ, changing their shape to move through tissue and modifying that tissue itself.

‘Cancer cells are adept at building nests in foreign tissue, by altering the structure and physical properties of the host organ’s supporting extracellular matrix, and recruiting local healthy cells. There are also hints that a primary tumour may send out chemical signals ahead of time to prepare the physical and chemical ground for the colonists.’

Ancient genes that lurk within

So, asked the researchers, were the cancer cells in fact unbundling a package of abilities and strategies that lie dormant in all cells and have been there for a very long time? Could it be indeed that the cancer cells were replicating what would have happened in the evolutionary past when individual cells first started to reach out and collaborate and form themselves into multicellular organisms – in the Proterozoic era, a billion years ago?

‘Evolution works by building on what came before,’ they noted. The genes that developed to shape the first multicellular groupings did not all become defunct over time.

‘Some were incorporated into the genomes of later, more sophisticated, organisms, and lurk inside human beings to this day. That’s because they still serve a crucial function. When an embryo develops, its genes lay down a body plan, starting with the most basic and most ancient features.

‘Human embryos, for instance, develop, then lose, gills, webbed feet and rudimentary tails, reflecting their ancient aquatic life styles. The genes responsible for these features normally get silenced as a later stage of development, but sometimes the genetic control system malfunctions and babies get born with tails and other ancestral traits. Such anomalous features are called atavisms.’

Switched on and re-activated

So could it be, they asked, that cancer tumours are a type of atavism, which appears as the result of something triggering ancestral genes, which normally are kept safely silent?

‘The reason that cancer deploys so many formidable survival traits in succession, is, we think, because the ancient genetic toolkit active in the earliest stages of embryogenesis gets switched back on, re-activating the Proterozoic developmental plan for building cell colonies. If you travelled in a time machine back one billion years, you would see many clumps of cells resembling modern cancer tumours.’

In other words, cancer cells are not selfish individuals whose priority is their own survival and reproduction, but members of a cooperative group, reaching out to each other to assist their mutual linkage.

‘Rather than cancers being rogue cells degenerating randomly into genetic chaos, they are better regarded as organised footsoldiers marching to the beat of an ancient drum, recapitulating a billion-year-old lifestyle.’

What could this mean for treatment? One point is that if the new theory is right, cancer cells are not continually coming up with innovative new strategies, for which new treatments must continually be found, but rather they are repeating standard patterns set long ago.

‘Cancer is not going anywhere evolutionarily; it just starts up all over again in the next patient. Although cancer may seem like a perpetually moving target, a given cancer has a strictly limited set of atavistic possibilities open to it. Thus, cancer is a limited and ultimately predictable adversary.’

What else could this mean for treatment? This will be the subject of Prof. Davies’s talk in the Conway Hall, London, on the evening of Wednesday 5 June. It is a bold new theory, says the magazine, and it suggests ‘a radical approach to therapy’.

For further background information

Cancer: The beat of an ancient drum? Paul Davies, The Guardian, 25 April 2011
Physics meets cancer: The disruptor. Nature, 2 June 2011
Cancer can teach us about our own evolution. Paul Davies, The Guardian, 18 November 2012
An interview with Dr Charles Lineweaver published in Science & Vie
Cancer tumors as Metazoa 1.0: tapping genes of ancient ancestors
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Physical Biology 8 February 2011, published online through NIH Public Access