Graphic: personalised cancer care

Scientists have begun a groundbreaking study of cancer that will “mix and match” tumours with drugs to develop personalised therapies for patients.

The £8.5 million, five-year project, by the British Sanger Institute near Cambridge and Massachusetts General Hospital in Boston aims to produce a catalogue of genetically distinct tumours and treatments. These could then be prescribed to cancer patients on the basis of DNA tests that predict which drug is most likely to work.

The research could herald a new era in cancer care, in which tumours with different genetic characteristics will be treated as separate diseases – even when they occur in the same part of the body. Two patients with breast cancer, for example, might get different drugs depending on the mutations carried by their respective tumours.

“From my perspective, this is really the future of cancer medicine,” said Professor Jeff Settleman, of Massachusetts General Hospital. “The phrase I like to use is personalised cancer medicine, where we select the drugs we give to patients according to the genomic features of their tumours.”

While more than 200 different types of cancer are already known, genetic investigations have shown that these can be divided into many more sub-types, each driven by particular patterns of abnormal DNA. This genetic variation can affect whether a drug will work: Herceptin, for breast cancer, is effective only when a certain mutation is present.

The initiative aims to identify other drugs that are useful against a particular genetic sub-type of cancer, even though they do not work as broad-spectrum treatments for all patients. It will investigate 1,000 colonies of cancer cells, each of which has already had its unique pattern of genetic errors mapped. These will be exposed to 400 chemical agents to identify which colonies are sensitive to which drugs. The results will then be cross-checked against the DNA profiles of the cancer cells, to highlight drugs that work when a particular combination of genetic defects is present. These could then be developed as promising therapies for patients whose tumours have that genetic fingerprint.

Professor Mike Stratton, of the Sanger Institute, said: “Cancer affects directly one in three of the world’s population. But we have new tools that we can bring to bear. Our emerging understanding of cancer mutations allied to our abilities to carry out large-scale research means we can develop screening techniques to find the most effective treatments for a whole variety of cancers.”

Many of the drugs that will be investigated have already been tested by pharmaceutical companies but were dropped because they did not have the broad effects that are required for a licence. The hope is that some of these can be “rescued” and used for a much smaller group of patients who show a good response. As many have already passed safety tests, these could rapidly progress to clinical trials.

“We’ve been noticing more and more over the years that for some drugs, while not everybody benefits, there is a subset of patients who are very strong responders,” Professor Stratton said. “This is a preclinical screen for that effect. There are drugs that could have been effective for some patients which have been lost to clinical practice because they don’t work in enough people. We hope we can get them back.”

The lung-cancer drug Iressa failed clinical trials because it did not have a sufficiently large effect on a general patient population, but 5 to 10 per cent of patients did very well. Drugs such as this could be reassessed.

Although cancer is often triggered by exposure to environmental carcinogens such as cigarette smoke, it is always, at root, a disease of faulty DNA. Genetic mutations, some induced by carcinogens, cause cells to start dividing excessively and spread through the body.

Ted Bianco, director of technology transfer at the Wellcome Trust, which is funding the study, said: “This significant and strategic project is aimed squarely at providing the first step towards tailored cancer therapy.”

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