NO CANCER is pleasant, but some are worse than others. On the scale of oncological nastiness, malignant melanoma is pretty close to the top. If caught early, when it is still a small, visible tumour on the skin (as illustrated above), melanoma can be excised completely. Once cells have broken away from the original tumour, though, and colonised other parts of the body, the outlook is grim: death within months, and no effective treatment.

That is why specialists gathered in Chicago for the annual meeting of the American Society of Clinical Oncology were crowded into the presentation by Stephen O'Day, from the Angeles Clinic and Research Institute in Los Angeles, and Steven Hodi, of the Dana-Farber Cancer Institute in Boston. These two researchers have been running a full-scale clinical trial of ipilimumab, an antibody that stimulates patients' immune systems to kill tumours. Their hope was that those tumours would include the secondaries spun off by melanoma. And that hope was fulfilled.

Though the prolongation of life offered by the antibody was not huge—3½ months, on average—it was real. And it was a first. Small-scale trials of other drugs have suggested such life extension. This is the only time, though, that tests to the highest scientific standard, that of randomised double-blindness on several hundred people, have demonstrated it beyond doubt for advanced melanoma.

Nor was this the only good news from the meeting. Another group, led by Bang Yung-jue of Seoul National University College of Medicine in Korea, showed that a drug aimed at a particular genetic mutation dramatically shrinks the tumours of people suffering from one type of lung cancer. Two other studies, meanwhile, confirmed that a similar approach to chronic myelogenous leukaemia continues to bear fruit.

Taking off the brakes

To demonstrate that their new drug works, Dr O'Day and Dr Hodi randomly assigned 676 people with advanced melanoma to one of three treatments: ipilimumab alone, ipilimumab plus an experimental vaccine, or the experimental vaccine alone. They discovered that those treated with ipilimumab or ipilimumab plus vaccine lived 50% longer than those treated with the vaccine alone—surviving an average of ten months compared with 6½. That was, however, just an average. Almost a quarter of those treated with ipilimumab were alive two years after treatment started. That compared with 14% of those treated just with the vaccine.

Ipilimumab is the first in a new class of drugs, called T-cell-targeted antibodies, that work by taking the brakes off the immune system and thus enabling the patient's own body to destroy cancer cells. Although some people experience serious—occasionally even fatal—autoimmune complications when this happens (one reason why the brakes exist in the first place), physicians think such side-effects can be managed, now that they know what to look for.

The drug works by binding to, and disabling, a protein called CTLA4, which is found on the surface of the immune system's T-cells. A second T-cell-related antibody, which binds to a different immune-suppressing protein, PD1, is being tested in smaller clinical trials. That antibody could eventually displace ipilimumab, if clinical trials show that it is equally effective and less toxic. Or, more likely, it could be combined with ipilimumab in order to deliver a double punch.

Investigators also want to combine ipilimumab with drugs that attack the tumour directly. The most promising is PLX4032, a molecule which blocks the action of the protein produced by a specific mutation of a gene called B-RAF. This mutation occurs in 60% of melanomas. Initial trials of PLX4032 suggest it may be as good as, or even better than, ipilimumab at improving sufferers' survival. A full-scale, double-blind trial is now under way.

A similar approach—of identifying one of the crucial mutations that has led to a cancer arising, and attacking it—is behind Dr Bang's lung-cancer treatment. The cancer concerned, known rather cryptically as non-small-cell lung cancer, is actually the most common form of the disease, accounting for about 80% of cases.

In 2007 a group of researchers discovered that the fusion of two normally independent genes, EML4 and ALK, into one aberrant gene seems to drive the formation of tumours. Since then it has been found that fused EML4-ALK causes 3-5% of all non-small-cell lung cancers (about 10,000 cases a year in America alone). A drug called crizotinib, which blocks the gene's activity in test-tube experiments, was already in development. At the meeting, Dr Bang reported the first clinical trial of crizotinib, on 82 patients whose tumours have the EML4-ALK fusion gene. Of those given the new drug, almost 90% showed shrinkage of their tumours and more than half saw those tumours shrink by at least a third. Moreover, three-quarters of those involved were still responding to treatment after six months.

Defusing cancer

That is significant, for one problem with cancer is that it is constantly changing. New mutations arise that nullify the effect of existing drugs, and the thing takes off again. Which is precisely what happens in the case of chronic myelogenous leukaemia. There is already a targeted treatment for this disease. Gleevec, probably the most remarkable anti-cancer drug of the past decade, disables the protein encoded by another fused gene, BCR-ABL. But Gleevac, too, can be bypassed by further mutations of BCR-ABL which allow the tumour cells to grow in the presence of the drug. By studying where exactly in the DNA sequence those mutations occur, and examining how Gleevec binds to the tumour-promoting protein that results, chemists have designed new compounds to avoid these problems.

Two of these compounds, Sprycel (dasatinib) and Tasigna (nilotinib) have been used for several years to treat patients whose disease has progressed even though they were taking Gleevec. However trials reported at the meeting show that the newer drugs also work better than Gleevec in recently diagnosed patients. Both induce faster and stronger responses than Gleevec does, though it is too early to say if the new agents actually prolong patients' survival.

The ultimate goal, then, is obvious. It is to block all of a tumour's avenues of genetic escape by developing drugs that deal with all the mutations that would allow such a break out. How many “all” is, is as yet unknown. A project run by the International Cancer Genome Consortium is looking into the matter, by studying tissue from 500 people suffering from each of 50 types of cancer. But if the escape routes really can be blocked then cancer, eventually, will have no hiding place and a diagnosis need not be the death-sentence it often is today.