x Abu Dhabi, UAESunday 23 July 2017

Cancer: to attack or contain?

Some cancer experts believe resources would be better used developing prevention and containment strategies.

Faced with a relentless enemy, experts committed to the war on cancer are questioning traditional strategies.
Faced with a relentless enemy, experts committed to the war on cancer are questioning traditional strategies.

Whatever his current concerns about the spiralling US health budget - now running at a staggering US$2 trillion (Dh7.3 trillion) a year - President Barack Obama has made clear his determination to press on with one pet project: the "war on cancer". Famously declared by President Richard Nixon in January 1971, it is a war which has brought a few victories, but many more disappointments. Over the decades, childhood leukaemia, breast cancer and testicular cancer have been rendered far less life-threatening, thanks to the discovery - largely serendipitous - of effective treatments. Even so, about 60 per cent of the 11 million diagnosed with cancer worldwide each year will succumb to this enemy within.

In February, Mr Obama unveiled an initiative aimed at "seeking a cure for cancer in our time" - and made clear his personal interest in victory, the disease having claimed the lives of both his mother and grandmother. While welcoming the US$1 billion (Dh3.7 billion) extra research funding, cancer experts were quick to play down talk of a cure for "cancer", pointing out that it is a catch-all name for a host of diseases in which healthy cells go haywire and needlessly proliferate.

At best, Mr Obama's injection of funds might speed the development of a few new therapies for a few forms of cancer. Last week, one group of cancer experts went further, arguing that the president's entire strategy was misguided. The US-based Cancer Prevention Coalition (CPC) called for more attention on the causes of the disease, pointing out that while cancer is a major cause of death "it is also one of the most preventable".

The CPC clearly has a point: smoking is the world's leading cause of cancers, most of which are incurable, but all of which are preventable. Yet if history is any guide, the CPC's call for a major strategy change will make little difference. In the search for new ways of tackling cancer, scientists have proved all too keen on hi-tech "weaponry" such as gene therapy and monoclonals - molecular "magic bullets" designed to home in on cancer cells like a guided missile. Few have lived up to their hype, but they are all more glamorous than plodding campaigns of preventive health.

Meanwhile, at the front line of the war on cancer, hospital doctors are reliant on therapies that are anything but glamorous. Most patients can expect to be given some combination of toxic chemotherapy compounds, radiation or surgery, which destroy billions of healthy cells in the hope of getting all the cancer cells. The appalling rate of collateral damage has long been justified by the fact that the survival of just one cancer cell can be enough to trigger a fatal relapse. Unlike a conventional enemy, even a single cancer cell can produce billions of copies of itself within months. Small wonder most cancer therapies offer only respite rather than a cure.

Faced with such a relentless enemy, even experts committed to the war on cancer are questioning the traditional strategy. They include Dr Robert Gatenby of the Moffitt Cancer Center in Tampa, Florida, who believes the answer is not to fight harder, but to fight smarter. Setting out his battle plan in a recent issue of the journal Nature, Dr Gatenby points to an analogy between fighting cancer and dealing with another living, self-replicating enemy: agricultural pests. For years farmers have been locked into an arms race against a host of pests, chemical weapons proving increasingly useless as the organisms evolve resistance against them. With final victory elusive, about 20 years ago agroscientists began experimenting with "integrated pest management", using pesticides to control infestation rather than eliminate it. Hundreds of invasive species are now successfully controlled with strategies that restrict population growth rather than eradicating them, Dr Gatenby says.

Could a switch from the current focus on eradication to one of containment also work with cancer? Dr Gatenby believes so, pointing to the similarities between invasive species and cancer cells. A few - like testicular cancer cells - aren't very adaptive and can be eradicated with aggressive chemotherapy. But the majority are all too successful at evolving defences, such as pumping anti-cancer drugs out of themselves and repairing radiation damage.

Evolving such ruses comes at a cost, however, sapping a cancer cell's ability to carry out other functions - like proliferating and invading other parts of its host. For example, lung cancer cells that survive the drug gemcitabine have proved less invasive than those sensitive to chemotherapy. And this, says Dr Gatenby, could hold the key to a new strategy against cancer: instead of trying to wipe out every cancerous cell, keep them pinned down.

In research published this month in Cancer Research, Dr Gatenby and his colleagues use computer models to investigate the effect of the strategy. The results suggest that overly aggressive therapy can prove lethally counter-productive. Before treatment starts, the most virulent cells are those yet to develop drug resistance. Aggressive therapy wipes these out, producing temporary respite - but at the price of allowing the less fit, more drug-resistant cells to proliferate, making the resurgent cancer untreatable.

This suggests that - as with pesticides - anti-cancer therapies should aim at managing the cancer cells, controlling the numbers of the drug-sensitive variety, which then keep their more devious counterparts in check. So much for theory: does it work? In the same paper, the team reports the results of experiments involving mice with ovarian cancer. Given conventional high-dose chemotherapy, the cancer rapidly retreated - only to surge back with lethal effectiveness. In contrast, when treated with drugs adjusted to keep cancer cells in check, the mice survived.

Dr Gatenby stresses that the results, while encouraging, are far from proof that containment is a viable strategy for human cancer patients. Questions remain over how to tailor the therapy, and whether it can be sustained for years on end. Nor is it clear whether it can help patients whose cancers have metastasised, spreading around their bodies. Certainly it does not reduce the need for cancer screening: many forms of the disease, including ovarian cancer, are lethal primarily because they produce few symptoms and are only discovered when it's too late to act.

Perhaps the biggest hurdle is not scientific but psychological. After years of being told victory is achievable, physicians, patients and even US presidents might have to accept that the most we can hope for in the war against cancer is an uneasy peace. Robert Matthews is a Visiting Reader in Science at Aston University, Birmingham, England