Why cancer is smart

This is my most recent piece on BBC Future, though another goes up tomorrow.

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Cancer is usually presented as a problem of cells becoming mindless replicators, proliferating without purpose or restraint. But that underestimates the foe, according to a new paper, whose authors argue that we’ll stand a better chance of combating it if we recognize that cancer cells are a lot smarter and operate as a cooperating community.

One of the authors, physicist Eshel Ben-Jacob of Tel Aviv University in Israel, has argued for some time that many single-celled organisms, whether they are tumour cells or gut bacteria, show a rudimentary form of social intelligence – an ability to act collectively in ways that adapt to the prevailing conditions, learn from experience and solve problems, all with the ‘aim’ of improving their chances of survival. He even believes there is evidence that they can modify their own genomes in beneficial ways.

Some of these ideas are controversial, but others are undeniable. One of the classic examples of a single-celled cooperator, the soil-dwelling slime mold Dictyostelium discoideum, survives a lack of warmth or moisture by communicating from cell to cell and coordinating their behaviour. Some cells send out pulses of a chemical attractant which diffuse into the environment and trigger other cells to move towards them. The community of cells then forms into complex patterns, eventually clumping together into multicelled bodies that look like weird mushrooms. Some of these cells become spores, entering into a kind of suspended animation until conditions improve.

Many bacteria can engage in similar feats of communication and coordination, which can produce complex colony shapes such as vortex-like circulating blobs or exotic branching patterns. These displays of ‘social intelligence’ help the colonies survive adversity, sometimes to our cost. Biofilms, for example – robust, slimy surface coatings that harbour bacteria and can spread infection in hospitals – are manufactured through the cooperation of several different species.

But the same social intelligence that helps bacteria thrive can be manipulated to attack pathogenic varieties. As cyberwarfare experts know, disrupting communications can be deadly. Some strategies for protecting against dangerous bacteria now target their cell-to-cell communications, for example by introducing false signals that might induce cells to eat one another or to dissolve biofilms. So it pays to know what they’re saying to one another.

Ben-Jacob, along with Donald Coffey of the Johns Hopkins University School of Medicine in Baltimore and ‘biological physicist’ Herbert Levine of Rice University in Houston, Texas, think that we should be approaching cancer therapy this way too: not by aiming to kill off tumour cells with lethal doses of poisons or radiation, but by interrupting their conversations.

There are several indications that cancer cells thrive by cooperating. One trick that bacteria use for invading new territory, including other organisms, is to use a mode of cell-to-cell communication called quorum sensing to determine how densely populated their colony is: above a certain threshold, they might have sufficient strength in numbers to form biofilms or infect a host. Researchers have suggested that this process is similar to the way cancer cells spread during metastasis. Others think that group behaviour of cancer cells might explain why they can become so quickly resistant to drugs.

Cancer cells are very different from bacteria: they are rogue human cells, so-called eukaryotic cells which have a separate compartment for the genetic material and are generally deemed a more advanced type of cell than ‘primitive’ bacteria, in which the chromosomes are just mixed up with everything else. Yet it’s been suggested that, when our cells turn cancerous and the normal processes regulating their growth break down, more primitive ‘single-celled’ styles of behaviour are unleashed.

Primitive perhaps – but still terrifyingly smart. Tumours can trick the body into making new blood vessels to nourish them. They can enslave healthy cells and turn them into decoys to evade the immune system. They seem even able to fool the immune system into helping the cancer to develop. It’s still not clear exactly how they do some of these things. The anthropomorphism that makes cancer cells evil enemies to be ‘fought’ risks distorting the challenge, but it’s not hard to see why researchers succumb to it.

Cancer cells resistant to drugs can and do emerge at random by natural selection in a population. But they may also have tricks that speed up mutation and boost the chances of resistant strains appearing. And they seem able to generate dormant, spore-like forms, as Dictyostelium discoideum and some bacteria do, that produce ‘time-bomb’ relapses even after cancer traces have disappeared in scans and blood tests.

So what’s to be done? Ben-Jacob and colleagues say that if we can crack the code of how cancer cells communicate, we might be able to subvert it. These cells seem to exchange chemical signals, including short strands of the nucleic acid RNA which is known to control genes. They can even genetically modify and reprogramme healthy cells by dispatching segments of DNA. The researchers think that it might be possible to turn this crosstalk of tumour cells against them, inducing the cells to die or split apart spontaneously.

Meanwhile, if we can figure out what triggers the ‘awakening’ of dormant cancer cells, they might be tricked into revealing themselves at the wrong time, after the immune system has been boosted to destroy them in their vulnerable, newly aroused state. Ben-Jacob and colleagues suggest experiments that could probe how this switch from dormant to active cells comes about. Beyond this, perhaps we might commandeer harmless or even indigenous bacteria to act as spies and agent provocateurs, using their proven smartness to outwit and undermine that of cancer cells.

The ‘warfare’ analogy in cancer treatment is widely overplayed and potentially misleading, but in this case it has some value. It is often said that the nature of war has changed over the past several decades: it’s no longer about armies, superior firepower, and battlefield strategy, but about grappling with a more diffuse foe – indeed one loosely organized into ‘cells’ – by identifying and undermining channels of recruitment, communication and interaction. If it means anything to talk of a ‘war on cancer’, then perhaps here too we need to think about warfare in this new way.

Reference: E. Ben-Jacob, D. S. Coffey & H. Levine, Trends in Microbiology 20, 403-410 (2012).