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Could circulating tumour cells be the swiss army knife of cancer markers?


Circulating tumour cells exist in tiny numbers in the blood of cancer patients, but they could be one of the best ways to track a patient’s disease, and they could also help researchers to develop new treatments.

Posted on 27 June, 2014 by Graham Shaw

Here at The Institute of Cancer Research in London, our scientists investigate cancer from all angles to discover new ways to diagnose, monitor and treat the disease. Our discoveries have led to innovative targeted treatments like the prostate cancer drug abiraterone, and we blogged recently about how we’re using the cold sore virus to kill cancer cells.

But once cancer has metastasised to other parts of the body in most cases it becomes extremely difficult to treat. Metastasis is the primary cause of death of patients with cancer – causing over 90% of cancer deaths.

Still, there is now increasing interest in using the cells cast off by tumours when they spread as a multi-purpose tool for cancer – the swiss army knife of cancer markers, if you like. Assessing these cells could potentially help in everything from monitoring disease progression to directing treatment strategies and monitoring their effectiveness.

Professor Johann de Bono, Professor of Experimental Cancer Medicine at the ICR and an honorary consultant at The Royal Marsden NHS Foundation Trust, has just published an interesting review on the subject in the journal Clinical Cancer Research. He, along with colleagues at the ICR, and in Spain and Switzerland, discuss how circulating tumour cells – or CTCs – are becoming essential tools in cancer research.

CTCs that have been shed by tumours into a patient’s bloodstream are the first signs that cancer may be spreading to other parts of the body. At these early stages there may be only one CTC for every 100 million cells in the blood – which makes accurately measuring CTCs a very difficult task.

But new technologies are now making this possible. Measuring CTC counts from blood samples can predict the seriousness of a patient’s cancer for several cancer types, including bowel, breast and prostate cancer. It can also assess if cancer treatments are producing an effect in patients, which could speed up the development of new therapies.

In a recent phase III prostate cancer trial carried out in the UK by Professor de Bono, researchers measured CTC counts from prostate cancer patients taken at multiple times during treatment with the drug abiraterone.

They found that when CTC levels dropped to under five for every 7.5ml of blood measured, there was a noticeable improvement in patient survival, which was seen from as early as four weeks after beginning treatment.

This is useful because at the moment, clinical trials must run for years to determine the effects of drugs on patients’ long-term survival, and CTCs could potentially provide the same sort of information much more quickly.

But the newest and most exciting application of CTCs is their use as molecular markers of a patient’s cancer.

CTCs as molecular markers

CTCs have the same genetic material as the tumour they came from, which means they share the same mutations driving tumour formation and growth. Analysing CTCs can tell scientists about the genetic make-up of cancer, without the need for invasive procedures like biopsies.

Molecularly characterising CTCs can tell us how treatments change antigens found on the cell membranes of CTCs, or how they reduce populations of CTCs with specific genetic markers. By measuring how CTCs change genetically before and after treatment regimens, researchers can see more clearly which molecular mechanisms are being affected by cancer treatments.

CTCs have already been used to test for a number of cancer-causing genes like HER2 and EGFR. Measuring changes in HER2 expression of CTCs from breast cancer patients could be an important way to detect disease recurrence or progression, while studies have shown that CTCs expressing EGFR can indicate the emergence of mutations leading to drug-resistance in lung cancer patients.

One day, we may be able to use CTCs to make treatment choices in the clinic, measuring the evolving characteristics of a patient’s tumour to select the most effective treatment at any given time.

But a word of caution about these promising, multi-purpose markers. Tumours are known to harbour populations of cells with distinct genetic mutations, so there are concerns that CTCs may not always represent the tumour as a whole or its more aggressive components.

Further research is needed, but as the technology becomes more sensitive and economical, measuring CTCs looks increasingly likely to become an essential tool for both cancer research and treatment.

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