Tracking tumours with blood tests

Advances in genetic technology could enable doctors to monitor cancer with a simple blood test, writes Arney.

CyberKnife treats cancer patients
There are more than 200 different types of cancer - each with different characteristics and treatments [EPA]

Cancer is a global issue, affecting more than 12 million people worldwide every year and claiming more than seven million lives. But it is also a deeply personal one, as patients and their families live through the hopeful highs and devastating lows of diagnosis and treatment. 

New research now shows us that cancer is also personal on a biological level. There are more than 200 different types of the disease – each with different characteristics and treatments – and within that, there is even more complexity. A 2012 study by Cancer Research UK scientists showed that there are 10 subtypes of breast cancer, defined by distinct genetic “fingerprints”. And our scientists recently pinned down similar fingerprints for three types of bowel cancer. 

What’s more, advances in DNA sequencing technology are revealing a multitude of gene faults (mutations) within an individual person’s cancer, meaning that their disease may be almost as unique as they are. While this genome-based approach is seen by many as the future of so-called “precision medicine”, the huge amounts of data it produces – as well as the challenges of analysing it – mean that real benefits for a large number of patients are still some way off. 

Finally, there is an added kicker. True to the principles that Charles Darwin laid out more than 150 years ago, cancer can also evolve inside the body. As the disease grows and spreads, cancer cells can pick up new gene faults and become more aggressive and resistant to treatment. Our researchers have discovered that even within a single tumour, cancer cells can be different on a genetic level. Tumours that have started growing in other places, such as the liver or lungs, are more varied still. And even if a particular drug wipes out 99 per cent of cancer cells, any pockets of survivors carrying drug-resistant mutations can spring into action and start multiplying out of control, as well as being stubbornly unaffected by that treatment. 

Being able to track the genetic twists and turns taken by tumours within an individual patient would be a huge benefit to doctors. For example, they would be able to tell what kinds of targeted treatments might be suitable – these are drugs designed to attack the products of specific faulty genes – and whether they are working, as well as being able to trace the rise of drug-resistant cells and identify the most suitable therapy to try next. 

For a long time it was thought that getting these answers would require that patients undergo repeated small operations to take samples of their cancer, known as biopsies, both at the original tumour site and places it has spread to. This is painful, costly and risky, especially for cancers buried deep in the body. And because of what we now know about the genetic variation even within single tumours, there is no guarantee that a biopsy would capture all the different types of cancer cells that are there. 

In the blood 

Luckily science has come to the rescue, as it usually does. Over the past couple of years, our scientists have been developing sensitive tests that can detect and analyse tiny fragments of DNA shed into the bloodstream by cancer cells as they die. This DNA reveals the genetic secrets of the whole population of tumours within the body, giving hope that there could soon be a “liquid biopsy” to allow doctors to track a patient’s cancer as it grows and changes. 

The first major step came last year, when scientists at our Cambridge Research Institute showed that they could detect these tiny DNA fragments, known as circulating tumour DNA, in blood samples from nearly 40 women with aggressive ovarian cancers. More importantly, they could use sensitive techniques to look for faults in specific genes in the DNA scraps, and even got a hint from one patient that it might be possible to track changes in cancer mutations over time. 

It's the missing piece of the jigsaw puzzle. We can now understand what happens during treatment, and how that affects the development of drug resistance.

by Professor James Brenton

In March this year, the same team published compelling evidence showing that monitoring circulating tumour DNA was the most effective way of measuring how breast cancer is responding to chemotherapy, compared to looking for whole cancer cells or certain molecules in the blood. Again, this was a small study, looking at just 30 women, and the researchers only focused on tracking a handful of specific gene faults. 

Then a month later, the researchers made an even bigger step forward, using similar technology to analyse all 20,000 genes in cancer cells from circulating tumour DNA fragments in the blood. 

Because of the challenges of doing this kind of work, the scientists studied just six patients – two with breast cancer, three with ovarian cancer and one with lung cancer. All of their cancers had spread to other parts of their bodies. Importantly, the research team collected samples before and after the patients had different treatments, so they could look at how the DNA from the tumour differed before and after treatment – including key gene mutations. 

The team found that the exact mutations present in the circulating tumour DNA subtly shifted over time, revealing how the cancer was changing and evolving in response to treatment. They could even spot the specific gene faults leading to drug resistance as they appeared. 

This has the potential to be a game-changer, and could rapidly lead to tests to help doctors monitor tumours and select the best treatment in the near future. The results show that it is possible to monitor how the whole cancer “ecosystem” within an individual patient is shifting over time on a genetic level, rather than relying on a handful of biopsies. 

As one of the researchers involved, Professor James Brenton, told us: 

“It’s the missing piece of the jigsaw puzzle. We can now understand what happens during treatment, and how that affects the development of drug resistance. This is a test simple enough to be scaled up to hundreds or thousands of patients. There are, of course, still unanswered questions, and we don’t know 100 per cent whether this applies to every patient, but certainly for most of the main cancer types – breast, bowel, lung, ovarian and so on – there’s good evidence that monitoring tumour DNA is feasible.” 

Where now? 

The next step is to scale up from the lab to the hospital as soon as possible, running clinical trials monitoring circulating tumour DNA in cancer patients to the high standards required within the UK’s National Health Service, known as CPA-standard testing. And then there is the rather more pressing matter of working out how best to exploit this new genetic information to bring real benefits to patients. 

And this is not the only area where blood tests for cancer are gaining ground. Cancer Research UK is providing more than 1 million pounds ($1.5m) to fund a new clinical trial of a blood test that could diagnose breast cancer earlier, and other projects are ongoing around the world. 

Although there are still a lot of issues to be ironed out with this kind of technology – the main one being the challenge of turning these discoveries into meaningful increases in cancer survival for patients whose disease has spread – there is increasing excitement and hope in the world of cancer research that real progress will be swift and soon. 

Dr Kat Arney is Science Information Manager at Cancer Research UK, the largest charitable funder of cancer research in the world. She also writes for the charity’s Science Update Blog