Around 90% of all cancer deaths occur because cancer cells that originated in one place were able to spread around the body, seeding tumours in other organs.
This transit of cancer cells is called metastasis, derived from the Greek “methistemi” meaning to change or displace. The term was coined by the French gynaecologist Joseph-Claude-Anthelme Récamier all the way back in 1829.
Nearly 200 years later, we still know very little about metastasis. Many analogies have been used to describe the process – for example the ‘shotgun’ effect where a tumour fires off ‘sticky’ cancer cells into the blood stream, or ‘immigration’ of cancer cells to new organs.
An English surgeon named Stephen Paget developed the ‘seed and soil’ analogy in 1889, based on his observations of breast cancer patients. He found breast tumours were 14 times more likely to spread to the liver than the spleen, implying that the way cancer cells spread is not random. Cancer cells that break away from the original tumour only ‘seed’ new tumours in organs that they are able to settle in – in fertile soil.
Not a one-way street
Each of these analogies implies a one-way movement of cells away from the original tumour site. However, new research conducted here at The Institute of Cancer Research in London and The Wellcome Trust Sanger Institute in Cambridge, has revealed the extent to which these unidirectional metaphors oversimplify what’s actually going on.
Scientists drill down to genetic root of prostate tumour development from The Institute of Cancer Research on Vimeo.
The new study, largely funded by Cancer Research UK, deciphered the DNA sequences of 51 tumours from 10 patients with prostate cancer, in order to look at the genetic changes that occur as the disease advances. This allowed scientists to map out a family tree of what happens when cancer spreads or becomes resistant to therapy in unprecedented detail.
For the first time using detailed sequencing, the researchers have shown that secondary tumours can themselves shed cells. These cells can travel round the body and themselves seed new tumours. Interestingly, the researchers also found evidence that the cells shed from secondary tumours can end up sticking to other tumours – painting a more complicated picture of metastasis than ever before described.
These findings have important implications for cancer treatment. Mutations that make cancer cells resistant to chemotherapy often arise in secondary tumours. If cancers have the ability to share resistant cells between tumours, it could mean more tumours could become resistant and a patient’s cancer could be even harder to treat.
Stopping the spread in its tracks
It’s not all doom and gloom. Researchers can use this information to design new and more targeted treatments for advanced cancer.
The research revealed that all of the tumours in a patient share common gene faults that occurred early on in the development of cancer. Drugs that target these faults could hit all of the tumours at once, blocking a cancer’s exits, preventing it from spreading and perhaps wiping it out entirely.
The ICR’s Professor Ros Eeles was one of the authors of the study. She said: “If we were able to stop the prostate cancer in its tracks, maybe after it only had one or two areas of spread, then we may prevent further spread. This idea of treating metastases intensively and early when there are only a few present is currently being tested in trials of high dose radiation to these areas.”
As well as gaining new insights into prostate cancer, this study has given us a deeper understanding of the evolutionary steps on the road to metastatic cancer. It describes a whole new pattern of spread that has important implications for cancer treatment.
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