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Sounding an early warning of cancer’s return


Tests for cancer DNA in the bloodstream can act as an early warning sign that drugs are no longer working, and could change the face of cancer treatment.

Posted on 19 October, 2015 by Dr Claire Hastings

For years scientists have been trying to develop faster and more sensitive tests for cancer that don’t involve invasive procedures being performed on the patient such as tissue biopsies.

This quest has focused on looking for cancer biomarkers in the bloodstream – molecules in circulation that act as ‘alarm bells’, indicating that there are cancerous cells present somewhere in the body.

A trip to the phlebotomist is all that’s required of the patient. Testing their blood could have two main uses – potentially to detect early signs of cancer in patients who haven’t yet been diagnosed with the disease, and more immediately to detect signs of relapse and drug resistance in patients who are under treatment for cancer.

Initially, scientists thought they were looking for protein or carbohydrate biomarkers. But recent advances in DNA technologies have led scientists to discover something curious about the cells in our body – they shed DNA into the bloodstream.

Cancer cells are no exception. As they multiply and form a tumour, some of the older cells will die. The DNA they release into the bloodstream is present in tiny amounts relative to the large amounts of normal genetic material in circulation – but modern technology has come up with a clever way of detecting it.

Scientists are able to use advances in genetic sequencing technologies to detect genetic mutations that are only present in cancer DNA, and use this information to separate out cancer DNA from DNA of healthy, non-cancerous cells.

Momentum has now picked up in developing the detection of circulating tumour DNA into ‘liquid biopsies’, which provide us with a detailed insight into the genetic make-up of an individual patient’s cancer. Here at The Institute of Cancer Research in London, we have made huge steps in the last few months.

Early warning of drug resistance

Professor Johann de Bono led some of the first studies into whether tests for circulating tumour DNA could assess if cancer drugs were working, using an analysis of phase I clinical trials conducted by the Drug Development Unit at the ICR and The Royal Marsden.

The team used a technique called next-generation sequencing to read the DNA code of tumour DNA from 159 blood samples in 39 cancer patients with different types of late-stage cancer.

The researchers found that by looking in detail at the tumour DNA in a patient’s bloodstream they could identify the best treatment for them. By taking serial blood samples they were able to find out early if the treatment was working, or if new DNA mutations had occurred that caused the cancer to become resistant.

This early warning of drug resistance in tumours meant doctors were able to switch treatments, giving patients a better chance of fighting the disease.

Previously, doctors would have relied on information from a tumour biopsy taken at the start of treatment – but that can’t give dynamic information about how cancers evolve, change and respond to drugs.

Professor de Bono said: “Our study used blood tests for DNA shed from tumours to help guide trial drug administration for that patient. We were able to monitor patients by taking multiple blood tests to build a picture of how a patient’s cancer is evolving in response to treatments. By monitoring patients in this way we could identify the mutations likely to prove lethal to that patient – and tailor treatment accordingly.

“Being able to monitor patients more thoroughly could decrease some of the concerns of phase I clinical trials, and could impact how we make treatment decisions in future.”

Detecting cancer relapse early

Recent research at the ICR and The Royal Marsden has also shown that testing blood samples for cancer DNA can detect tiny numbers of tumour cells that were either left behind after surgery, or that were resistant to chemotherapy.

This method can detect these leftover cancer cells as early as eight months before they would be visible in hospital scans.

Researchers took tumour and blood samples from 55 breast cancer patients with early-stage disease who had received chemotherapy followed by surgery, and who had potentially been cured of their disease. By monitoring patients with blood tests taken after surgery and then every six months in follow-up, the researchers were able to predict very accurately who would suffer a relapse.

Dr Nick Turner, who led the research, said: “We have shown that a blood test has the potential to accurately predict which patients will relapse from breast cancer – much, much earlier than we can currently.

“It will be some years before the test could potentially be available in hospitals, but we hope to bring this date closer by conducting much larger clinical trials. There are still challenges in implementing this technology, but our method is relatively cost-effective and the information that it provides could make a real difference to breast cancer patients.”

What’s next?

Researchers at the ICR, and all over the world, are continuing to work on developing quicker, cheaper and less invasive tests for cancer. Dr Turner is trialling his breast cancer blood test in a larger group of patients as early as next year.

Professor Paul Workman, Chief Executive of the ICR, said: “We are moving into an era of personalised medicine for cancer patients. Blood tests that detect DNA shed from tumours could help us stay a step ahead of cancer by monitoring the way it is changing and picking treatments that exploit the weakness of the particular tumour. It is really fantastic that we can get such a comprehensive insight about what is going on in the cancer all over the body, without the need for invasive biopsies.

“Studies like this also give us a better understanding of how cancer changes to evade treatments – knowledge we can use when we are designing the new cancer drugs of the future.”

Detecting tumour DNA in the bloodstream could be the patient-friendly early warning system scientists have been searching for – one that looks likely to change the way we treat cancer in future, and ultimately save lives.


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