First trace-back of a tumour unveils how cancer spreads

20170517120000, Brenda Lau
There could be other factors that contribute to how an extrapolated rate of metastasis occurs.
There could be other factors that contribute to how an extrapolated rate of metastasis occurs.
Last month, thousands of Britons were diagnosed with cancer only after three visits to the GP, according to researchers from University College London, the University of Cambridge, the University of Exeter and Public Health England.

The researchers pointed out that some of these people had cancers that were more difficult to diagnose, such as lung cancer and myeloma, whereas others had symptoms at a younger age than expected.

For men and the elderly, it was suggested that there may be a range of practical, emotional and health barriers that delay them from seeking help. Others were misdiagnosed or were refused biopsies after an abnormal test result.

A recent study done by the Institute of Cancer Research seeks to answer some questions of why signs and symptoms can be missed.

A rare side effect turned for the better of research

In 2008, a man was diagnosed with bowel cancer, which later metastasised, spreading into other areas of his body. After the primary cancer was surgically removed, a nodule was discovered in the man's lung. Nicola Valeri, head of the study also suspected the nodule would be cancerous but decided to monitor it before any surgery was performed.

Three years later in 2011, a biopsy was performed, revealing that the nodule was indeed a secondary tumour - it was subsequently removed.

However, the biopsy had a rare side effect - it left behind a trail of cells from the tumour as doctors withdrew the needle. The cells then turned into another secondary tumour in the patient's chest wall.

The tumour was not discovered until two years later and was found to occupy the precise track from where the needle had been inserted and removed. Therefore a fair assumption was made that the tumour originated on the day of the biopsy.

This allowed Valeri and his colleagues to use it as a timestamp, alongside a genetic analysis of all the tumours the man developed before dying to understand how the cancer progressed over his lifetime.

The mutations that were developed, the rate of change and the progression of the disease could all be traced back to the time of its origins - and the results were somewhat surprising.

Dormant years could be taken advantage of

Analyses showed that the primary colon cancer actually began five to eight years before it was diagnosed. A year after it developed, it began metastasising and travelled to the lung and the thyroid.

The biggest surprise to the researchers was that the cancer spread very quickly from the bowel to the lung and thyroid, yet all three of these tumours remained dormant for many years instead of growing and spreading.

"It suggests that sometimes, there's a large time window to make diagnosis early and disrupt metastatic spread," he said, "It means there might be periods of years where we could intervene."

Previous studies done by Cancer Research UK in October 2014 also showed that cancerous cells usually sit dormant in the lungs for decades before they diversify and spread.

The possibility of other factors responsible for increased metastasis

The analysis also revealed important clues as to why the cancer spread so fast was dormant for a few years before becoming aggressive, adding on to a study also by Cancer Research UK in January 2014 that showed that cancer reorders the genome by evolving in large leaps or "macromutations" suddenly.

But for this patient, although a known mutation to promote the spread of cancerous cells occurred early on, this did not appear effect the development of subsequent metastases. The tumours also did not have any large genetic alterations that make cancers most aggressive such as the loss or duplication of chromosomes.

This presents a possibility that there are other factors present that contribute to how an extrapolated rate of metastasis occurred, which could lead to a better understanding of a cancer's behaviour. This could lead to development of new treatment strategies to target tumours with drugs at the right time for maximum effect.

"Studies like these and the tools they use will be critical in the future management of cancer," says Carlo Maley of Arizona State University in Tempe, who specialises in cancer evolution and contributed to the analysis. "I usually think of metastasis as the start of a runaway process that kills us." MIMS

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