x Abu Dhabi, UAEWednesday 26 July 2017

New tactics needed in war on cancer

A permanent cure for some cancers may be impossible. But that doesn't mean the situation is hopeless.

Front-line troops from a decades-long war will roll into Abu Dhabi on Tuesday, amid their latest efforts to engage the enemy across the Emirates. But as its decidedly non-macho moniker suggests, the Pink Caravan has an unusual adversary: cancer.

Set up three years ago by the charity Friends of Cancer Patients, the Pink Caravan is confronting breast cancer by combining education with medical screening.

To date, its specialists have examined more than 20,000 women (and several thousand men, as they too sometimes develop the disease). How many lives they have saved is hard to say, though early detection is seen as critical to winning the war against cancer.

After all, the sooner the "weaponry" of anti-cancer drugs can be applied, the better the chances of victory. Early detection cuts five-year mortality rates from a fearsome 85 per cent for late-stage disease to just 7 per cent.

Certainly, in the case of breast cancer - notoriously common among young women in the UAE - doctors have some impressive drugs in their armamentarium. But doctors are still far from total victory with this disease - let alone the 200-plus other cancers to which humans fall prey. Now growing numbers of medical scientists are wondering if the time has come to give up the old metaphors of "wars" and "victories" - and not only for cancer, but for other diseases as well.

The rethink follows ever-increasing evidence that in many cases, a permanent cure may never be achievable. Yet far from being defeatist, this acceptance of the limitations of medicine is breaking an intellectual logjam. In particular, it is leading to the growing awareness that "incurable" need no longer be a synonym for "without hope".

Such a seismic shift in attitude has already taken place with respect to another much-feared killer.

Like cancer, Aids became the focus of a "war" of which the aim was nothing less than final victory in the form of a permanent cure.

And at first there seemed hope of finding one. The virus responsible was identified in 1983, and within a few years a promising anti-viral drug, zidovudine (often called AZT), was in clinical trials. Yet with patients given the drug still succumbing with depressing speed, initial optimism gave way to gloom.

HIV, the virus responsible for Aids, proved far more resilient than anyone expected, constantly evolving to evade attack. But in the mid-1990s, medical scientists began to realise that while a cure may be elusive, it may at least be possible to contain the virus.

This led to the emergence of so-called Highly Active Anti-Retroviral therapy (HAART), in which HIV is hit by several anti-viral drugs simultaneously.

The effects were dramatic, with up to 80 per cent declines in death rates. While not cured, those patients able to sustain the demanding drug regimen typically keep HIV at bay for an extra 15 years.

Now cancer treatment may benefit from a similarly radical re-think. For while there have been many impressive results from drug therapy - notably childhood leukaemia and testicular cancer - the fact remains that most cancers continue to defy the quest for cures. Could containment be the best approach for these as well? Some cancer experts think so, not least because cancer cells are even more adept at dodging drugs than HIV.

While there are many different types, all cancers begin with a single renegade cell whose genes have gone wrong, promoting uncontrolled replication. The result is exponential growth in the number of cancer cells - which run into billions by the time they are detected by screening. But these descendents of the original cell aren't all exact copies; they too have undergone their own mutations, creating a vast and varied community of cancer cells, all with their own quirks.

Anti-cancer drugs may kill off many or even most of them, but chances are some will have traits allowing them to resist the drug - and it only takes one to do so for the cancer to start all over again. Worse, those cancer cells that do survive face less competition from others and are thus able to thrive, in a deadly cellular version of Darwinian evolution.

The implications of all this for cancer therapy are now becoming clear: in the war on cancer, doctors need to fight smarter.

One of the leading proponents of this strategy is Dr Robert Gatenby of the Moffitt Cancer Centre in Tampa, Florida. He draws analogies between cancer cells and agricultural pests. Some aren't very adaptive and can be eradicated with aggressive treatment - like ant infestation. But most are highly effective at evolving defences and need a smarter approach.

One possible line of attack centres on exploiting the fact that in acquiring drug resistance, cancer cells become less adept at growing and spread through the body. In 2009, Dr Gatenby and his colleagues used computer models to show that overly aggressive drug therapy can thus prove lethally counter-productive.

This paradoxical finding may explain why conventional high-dose chemotherapy can trigger a lethal resurgence of the disease.

It also fits in with experiments by an international team of researchers, reported last month in the journal Nature. In studies involving mice, the team found that skin cancer cells not only evolved resistance to drug treatment, but actually thrived on it.

This has led the team to propose that drugs may work better if patients are left untreated for a while, to slow the proliferation of cancer cells that thrive on the drugs.

This, in turn, points to a more long-term view of cancer treatment, where the disease is not "attacked" for months, but contained for years - even decades.

We can expect more counter-intuitive insights as this new approach to the war on cancer gathers momentum. Whether they will be put into action by today's "troops" in the medical profession, long used to talk of a final victory, remains to be seen.

 

Robert Matthews is visiting reader in science at Aston University, Birmingham, England