Not so ‘smart’ drugs

Targeted medicines hit wide of the mark. By Pat Thomas

Not long ago a group of physicians, bioengineers, drug manufacturers and marketing men met in Atlanta. The occasion was the annual and highly influential American Society of Clinical Oncology (ASCO) conference.

The yearly ASCO conference is an important marketing platform for manufacturers of cancer drugs. If you can sway the minds of the assembled investors and reporters with good news about the latest pharmaceutical miracles, you can guarantee yourself a profit-making drug.

This year the talk was all about ‘smart bombs’ – targeted drugs, some of which use nanoparticle delivery systems, that promise to kill the cancer and leave the patient standing. Cancer smart bombs are medicine’s latest effort towards a more ‘personalised medicine’; and yet if this latest evolution of the concept of the body as a battleground is anything to go by, medicine has moved so far away from the personal that it may never find its way back.

Targeted cancer drugs are the result of the combined efforts of geneticists and bioengineers, and according to most pundits they are a sign of progress.

Most prescription medicines are now effective for fewer than half of the people who take them – and the side-effects can be worse than the illnesses. The shift from non-specific systemic drugs that have a broad-brush effect and can be taken by millions of people, to those tailored to a minority with a specific genetic profile, is seen as a way of reducing adverse effects – which hospitalise a quarter of a million people in the UK and more than two million in the US each year. Fewer adverse effects also means less potential for being sued – a bonus for litigation-weary doctors and insurance companies.

Unfortunately, before most of these smart bombs can get past a full set of clinical trials, the cracks inevitably begin to show. Smart bombs, it appears are not so smart after all.

The breast cancer drug Herceptin, manufactured by Roche, is a good example. From the moment it hit the market it was clear that there were problems. Clinical trials showed that around four per cent of women sustained severe heart damage while taking the drug. A further, but as yet unquantified, number of women were believed to experience mild to moderate heart symptoms. Since there is still no long-term data on Herceptin it is impossible to say if these figures are an under- or overestimate, but what is clear is that they are not a fluke. Recently another targeted cancer drug, Glivec, manufactured by Novartis, was also found to damage the heart.

When bad news like this hits the press, Big Pharma’s spin doctors and the physicians they pay to endorse their products will often feign shock and say that such adverse effects simply could not have been predicted until the drug was being used widely. This is not true and such a disingenuous attitude to human health is simply not acceptable.

Consider just one example of the heart and cancer link. Back in 1999, scientists at Emory University discovered a new family of enzymes that play an important role in generating the abnormal cell growth that occurs both in cancer cells and in some forms of cardiovascular disease. These enzymes produce what are known as reactive oxygen species, which function as potent growth promoters inside cells, instructing cells to divide more rapidly. In the case of cancer, rapid and uncontrolled cell division leads to tumour formation. In cardiovascular disease, abnormal cell growth leads to the formation of plaques, seen in hardening of the arteries (atherosclerosis) and in thickening of the blood vessel walls, which causes high blood pressure.

Heart disease and cancer, then, are the results of very similar processes; and targeted cancer therapies are a prescription for problems, because they draw battle lines that the body simply does not, indeed cannot, acknowledge. In the body, as opposed to in the lab, any drug that targets specific enzymes in the tumour cell will most likely target the heart as well.

It is worth remembering that while conventional medicine persists in thinking of tumours as foreign objects of mysterious origins, a cancerous growth is a part of the body and an extension of normal bodily processes.

At a very basic level, cancer – the result of uncontrolled duplication of cells – represents the extreme end of a spectrum of natural physiological functions. It is similar to the process that turns a blastocyst into an embryo and then a foetus and then a child. It is the process that takes place in cells and tissues to help heal cuts and wounds. Seen in this way, what we call ‘cancer’ is really just an arbitrary label given to a normal biological process, taking place at the wrong time and in the wrong place and in a body that has, probably for multiple reasons, failed to keep it in check.

In Europe, where autopsies are still common, it is not unusual for coroners to find people carrying undetected cancers in their bodies. These cancers are generally kept in check by the body, often for years, and have posed no threat to the carrier. Until we understand why some cancers progress while others do not, all the smart bombs on the planet will not help us cure cancer. But we will never gain this level of understanding until we get back to seeing the body as an integrated and holistic system.

At present, most of the pharmaceutical smart bombs are cancer treatments. But already bioengineers are producing similar types of drugs to treat heart disease. Drug manufacturers are salivating at the prospect. It’s worth asking: if cancer drugs can cause heart disease – how far are we from a future where targeted heart disease drugs can also cause cancer?