US researchers step closer to personalised cancer care

Different cancers contain different types of DNA damage

US scientists today report that they’ve identified ‘personalised’ genetic markers in the blood of two bowel cancer patients using a cutting-edge technique called massively parallel DNA sequencing, and used these markers to monitor the patients’ cancers during treatment.

The team say that their new technique – dubbed PARE (‘personalised analysis of recombined ends’) – is a big step towards ‘personalised’ cancer care – a long-held goal for cancer research.

Their work is published in the journal Science Translational Medicine.

Although there’s still work to do to refine the technique and make it quick enough and – importantly – cheap enough for routine use, it’s very exciting news.

Monitoring treatment

As well as developing new treatments, cancer researchers worldwide are trying to work out how best to monitor how well a treatment is working, or whether a patient’s cancer is coming back.

Currently, there are various ways to do this, including taking tissue samples or using scans like PET and MRI. But scientists can also look for ‘biomarkers’ – tell-tale signs of the disease in the blood or other bodily fluids.

Perhaps the best known cancer biomarker is prostate-specific antigen, or PSA – the basis of the controversial PSA prostate cancer test, which we’ve extensively discussed on this blog. But several others exist too, such as the CA125 test, which is used to monitor ovarian cancer, and researchers are working hard to find more.

A common feature of – and problem with – tests like PSA is that they rely on molecules present in all of us, and so don’t take into account the fact that we’re all genetically unique. Different people produce different levels of different biomarkers – so it’s sometimes hard to interpret results.

Even more problematically, tumours can arise via a multitude of random genetic alterations and mutations – so each one is unique too. Not only do different people have different ‘background’ biomarker levels – different tumours affect these levels in different ways.

But perhaps this individuality could be used to our advantage. Since every patient’s tumour is genetically distinct from the rest of the patients’ cells, it should be possible to track and monitor it – to spot the odd one out from the group.

For some types of cancer, we can already do this. It’s now possible to monitor the progress of certain leukaemias and lymphomas – cancers of the blood – by using their genetic signatures as the basis of a test to follow the success of treatment. And this has revolutionised the management of these diseases.

But by their very nature, these cancers are present in the bloodstream in high quantities. Unfortunately, so-called ‘solid’ tumours like breast, bowel, lung and prostate cancers have proven much more difficult to track. And that’s why this new research is generating such excitement.

What did the researchers do?

The new research wouldn’t have been possible without a new technique called massively parallel DNA sequencing.

Unlike previous DNA techniques, massively parallel sequencing allows scientists to take a cell sample and analyse all the DNA in it in at once. It’s an improvement from earlier laborious techniques of analysing things one gene at a time, or by homing in on pre-determined ‘hot-spots’ to look for changes.

Professor Victor Velculescu, a researcher based at the Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland, and his team used massively parallel sequencing to examine DNA from various tumour samples, building ‘maps’ of exactly where their individual errors were.

They also used other ‘traditional’ sequencing approaches to confirm that their maps were correct, and found that the maps generated by massively parallel sequencing were not only accurate but far more detailed and informative than those generated by other methods.

From DNA analysis to tumour markers

Now they were ready to put these maps to use. Having pinpointed unique faults in tumour samples taken from two bowel cancer patients, the researchers developed a specific DNA test for each patient’s tumour, based on a widely used lab technique called PCR.

They then used these tailored tests to look for signs of the tumours in the two patients’ blood as they went through treatment. The stunning finding was that the team were able to pick out telltale signs of cancer DNA in blood samples, despite the presence of large amounts of ‘normal’ DNA.

In their paper, the researchers describe how they tested blood samples from one patient six times – twice before treatment, three times after surgery but before chemotherapy, and once after chemotherapy. They were able to watch the tumour DNA levels drop after surgery, rise again as the remnants of the cancer grew back, then drop almost to zero after chemotherapy.

But the levels never quite dropped to zero, since the patient’s cancer had spread to their liver – a finding that highlighted how sensitive the test was.

What happens next?

The researchers only tested the new technique in two cancer patients, so it will need to be put through its paces on a much larger scale, with a variety of different tumour types, to make sure these principles hold true. And cost is still very much an issue. Although massively parallel sequencing is getting cheaper, each ‘map’ produced in this study cost about $5000 (over £3000) to produce – too expensive for routine clinical use.

Nevertheless, experts agree that this is a highly promising area. Daniel MacArthur, author of the Genetic Future blog and a geneticist at the Wellcome Trust Sanger Institute in Cambridgeshire, told us that he expects approaches like this to “become routine” for cancer patients in the future.

He says, “The costs of massively parallel sequencing are dropping rapidly, and this study provides a glimpse of the future of personalised cancer treatment.”

Our chief clinician Professor Peter Johnson agrees that the new results are an exciting step forward. “The detection of DNA changes, unique to individual cancers, has proved to be a powerful tool in guiding the treatment of leukaemia,” he told us.

“If this can be done for other types of cancer like bowel, breast and prostate it will help us to bring new treatments to patients better and faster than ever.”

The future is personalised

Nearly a decade after the publication of the complete human genome, we’re still a way from being able to offer patients truly tailored cancer care. But genetic technology continues to progress at a dizzying rate. For example, in December we reported the news that scientists had used massively parallel sequencing to compare cancerous cells to their disease-free counterparts in unprecedented detail.

This breakthrough was exciting for cancer researchers, and gave them a much more sophisticated set of tools with which to study the disease. But we cautioned at the time that it would take a while for this line of research to yield concrete benefits for patients.

The research published this week takes us another step closer to a world of personalised cancer care. But it’s only through the continued investment in cancer research – and the continued hard work of research scientists around the world – that we’ll ever reach this destination.

Henry

Reference:

Leary RJ. et al (2010). Development of Personalized Tumor Biomarkers Using Massively Parallel Sequencing; Science Translational Medicine 2(20)

Rogers, Y., & Venter, J. (2005). Genomics: Massively parallel sequencing Nature, 437 (7057), 326-327 DOI: 10.1038/437326a