Colon cancer: here are the biological differences that make it more aggressive in young people
A biological map has been unveiled that could help identify new therapeutic targets, improve our understanding of the disease and develop more personalised approaches
Key points
Colorectal cancer is changing. Once thought to affect only adults and the elderly, it is now being diagnosed with increasing frequency in people who are not yet 50. In the United States, between 2013 and 2022, diagnoses in this age group rose at a rate of around 3 per cent a year. However, colorectal cancers diagnosed before the age of 50 may have different biological characteristics to those that develop later in life. In short, it is not simply a case of the same disease occurring earlier.
A resolution never before achieved
This is confirmed by a study recently published in Nature Medicine, which has explored the biology of colorectal cancer in unprecedented detail, analysing the genetic activity of over 850,000 cells and the tumour microenvironment – that is, the tissue surrounding them.
Researchers at the Broad Institute of MIT, Harvard Medical School and Dana-Farber Cancer Institute (USA) examined 189 colorectal tumours, 54 of which were diagnosed before the age of 50 and 135 after.
In this way, they were able to identify, in the tumours of younger patients, a higher proportion of supporting cells and specific molecular signals (the so-called ‘signature’ of the tumour) that could have a negative impact on the behaviour of the disease.
In particular, in carcinomas of the most common subtype (those with microsatellite stability), a higher proportion of stromal and supporting cells was present in younger patients compared with neoplastic cells. This is an interesting difference because the stroma is not merely a capsule surrounding the tumour; it can, in fact, play an active role in influencing tumour growth, invasiveness and response to treatment. In other cancers, such as pancreatic cancer, a higher stromal component has been associated with resistance to chemotherapy. However, it has not been demonstrated that this mechanism also explains the behaviour of the juvenile tumours analysed.
The ‘dark web’ of RNAs: a possible new avenue of research
The authors of the study also observed increased activity in the tumours of young people of certain long non-coding RNAs – molecules that regulate gene expression without directly encoding proteins.
Some of these belong to as yet poorly understood regions of the ‘transcriptome’, known as ‘dark’ RNAs. Alongside these, molecular signals consistent with increased communication between cells involved in migration and invasion processes have also been identified.
