New research into the genetic and molecular features of cancers that have spread has revealed the diversity of these tumours and the immune cells within.
The US team behind the research suggest that the findings could help guide treatment decisions in the future and identify patients who might benefit from certain treatments, such as those that target the immune system.
“Our hypothesis is that we could use this to help determine who is likely to respond to immunotherapy,” said lead researcher Dr Arul Chinnaiyan from the University of Michigan Comprehensive Cancer Center.
As cancers develop and progress, they can spread to other parts of the body and become more difficult to treat. During this process of cancer evolution, the genetic characteristics of the tumours may also change. It’s the features of these later stages of disease that the researchers focused on.
The team read the DNA, or genomes, from cells in healthy tissue and tumours that had spread (metastasised) in over 500 patients with more than 20 types of cancer. They also looked at which genes were switched on or off in the cancer cells, and profiled the immune cells that were inside the tumours.
The scientists then compared this information with data on early stage disease available from a vast database called The Cancer Genome Atlas.
They found that the metastases were very genetically diverse and generally had more faults in their DNA than early tumours. The team also found that more than 12% of the patients sampled had cancer cells carrying inherited faulty genes that could affect the likelihood that their disease spreads.
The majority of these faults were found within genes that fix damaged DNA. As scientists have developed drugs that can target this process, this finding may have implications for treating patients in the future, the authors claim.
“One of the main take home messages from this study is that metastatic cancer is extremely diverse,” said Professor Laura Machesky, from the Cancer Research UK Beatson Institute, who was not involved in the research.
“The group has discovered new genetic faults in metastatic disease, although the function of many of these needs to be characterised.
“The finding that some people’s genetics might make them more or less likely to develop metastatic disease could offer an exciting opportunity for genetic profiling and targeted treatment during very early stages of cancer.”
The US team was also able to profile the immune cells that had made their way inside the tumour, which they say could indicate those patients who might benefit from treatments that target the immune system. The findings have been published in the journal Nature.
Professor Andrew Biankin, a Cancer Research UK-funded expert on genetics from the University of Glasgow, said: “We have made major leaps in our understanding of the genomes of cancer over the last decade, unpicking the very roots of what makes cancer tick – though there is still much to learn. We understand a lot about the early stages of cancer, but this is the first study to really take a deep look at a significant number of metastases, a characteristic of advanced cancer.”
He added that studying how cancers evolve, particularly through treatment, is crucial for drug development as therapies that can be effective against early cancers might not work in advanced disease, or after previous treatments.
Robinson, D. R. et al. (2017). Integrative clinical genomics of metastatic cancer. Nature. doi:10.1038/nature23306