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Using the seeds of cancer to guide treatment strategies

In 1869, pathologist Thomas Ashworth noticed some unusual cells in the blood of a patient who had died of cancer. The cells didn’t look like normal blood cells – instead, they were similar in appearance to those found in the numerous solid tumours present all over the patient’s body. Ashworth speculated that perhaps the cells came from the existing tumours, and could help explain the distribution of the patient’s multiple lesions.

Scientists now believe that these so-called circulating tumour cells play a key role in metastasis – where cancer spreads to other parts of the body. They act as ‘seeds’ – breaking away from the primary site of cancer and colonising other sites in the body. Through their role in the progression of cancer, circulating tumour cells have become an increasingly useful tool in cancer medicine as a measurement of a patient’s state of disease, or ‘biomarker’.

Prostate cancer cell. Photo: Mateus Crespo/Professor Johann de Bono, the ICR
Prostate cancer cell (image: Mateus Crespo/Professor Johann de Bono, the ICR)

Professor Johann de Bono – Professor of Experimental Cancer Therapeutics at The Institute of Cancer Research, London, and an honorary consultant at The Royal Marsden NHS Foundation Trust – has seen the promise in using circulating tumour cells as multi-purpose biomarkers. His team was the first to study circulating tumour cells in early drug trials in advanced prostate cancer, and is now investigating using them as an intermediate endpoint of overall survival in this disease.

Professor de Bono’s group recently showed that measuring the numbers of circulating tumour cells in the blood predicted which men were benefitting least from abiraterone – a prostate cancer drug – after as little as 12 weeks of treatment.

“A blood test could be developed that measures the number of cells shed from prostate tumours into the bloodstream, which can act as an early warning sign that treatment is not working,” Professor de Bono explains.

“Under the current clinical trial system, new drugs must show that they keep men alive for longer than the existing drugs, which means many years of follow-up and often many of the patients on the trial have died before conclusive results are achieved. So this type of information is useful because circulating tumour cells could potentially provide the same sort of information much more quickly. If further studies prove successful, we envisage doctors in the clinic being able to switch patients to alternative treatments earlier than is currently possible.” 

Another exciting avenue for circulating tumour cells is their use as molecular markers of a patient’s cancer. “Because circulating tumour cells have the same genetic material as the tumour they came from, they share the same mutations driving tumour formation and growth,” says Professor de Bono. “Analysing these cells can tell us about the genetic make-up of cancer, without the need for invasive procedures like biopsies.

"Molecularly characterising circulating tumour cells can give us insight into how treatments change antigens – proteins found on the cell membranes of cells – or how they reduce populations of circulating tumour cells with specific genetic markers. By measuring how these cells change genetically before and after treatment regimens, we can also see more clearly which molecular mechanisms are being affected by cancer treatments.”

Professor de Bono’s work could ultimately lead to doctors measuring the levels and molecular characteristics of circulating tumour cells at multiple time points along a patient’s cancer journey. This could potentially help in everything from tracking a patient’s disease progression to directing treatment strategies and monitoring their effectiveness.

Currently, to assess whether a drug is working doctors must rely on techniques such as imaging or biopsy, which are slow to show results and may be impractical or uncomfortable for patients, or prostate-specific antigen (PSA) testing, which can be unreliable. A blood test could be used to confirm that the drug is benefitting a particular patient – or if not, they could be moved quickly to an alternative therapy. This would mean that patients would suffer fewer side-effects from unnecessary treatments and that less money is wasted on expensive new drugs that are not working.

Over the succeeding 140 years or so after Thomas Ashworth’s discovery, cancer research has demonstrated the fundamental role that circulating tumour cells play in metastatic cancer. Further research is needed, but as the technologies to measure circulating tumour cells become more sensitive and economical, they are likely to become an increasingly important tool for both cancer research and treatment.


prostate cancer
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