Scientists Discover Colorectal Cancer Has Four Distinct Subtypes

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Colorectal cancer can be divided into four distinct subtypes, each with its own set of biologic characteristics. These findings from a major new study were reported in Nature Medicine (2015; doi:10.1038/nm.3967). The research could allow doctors to treat each type of colorectal cancer differently and it may drive the design of drugs targeted to each type.

Scientists at The Institute of Cancer Research, London, United Kingdom, alongside colleagues at research institutes in the United States and Europe, brought together the world's largest set of data on colorectal cancer to classify tumors into groups.

Researchers believe that the most immediate implication of their findings will be to help identify patients at risk of developing more serious, fast-growing disease that requires more intensive treatment.

The study combined data from 3,443 patients with colorectal cancer from all over the world to form the largest collection of molecular and clinical data on the disease ever assembled, including genetic mutations, gene activity, immune system activation, cell metabolism, cancer cell type, and ability to invade neighboring tissues.

They aimed to group colorectal cancers using mathematical algorithms that combined all these parameters, with the goal of improving on various existing attempts to classify types of the disease based on smaller datasets.

The scientists found that 87% of colorectal cancers could be robustly assigned to one of four groups. Tumors within the four consensus molecular subtypes (CMSs) each had a pattern of irregularities that could leave them vulnerable to the same treatment strategy.

One particular type of colorectal cancer, CMS4, was often diagnosed late (stage III and IV), had high levels of metastasis to other sites in the body, and had significantly worse survival rates than the other types.

Survival rates for patients with type CMS2 colorectal cancer were much better even if the cancer had relapsed.

“Our study has identified four distinct types of bowel [colorectal] cancer, each with a definite set of genetic and biological characteristics, and some of which are more aggressive and more likely to be fatal than others,” said study co-leader Anguraj Sadanandam, PhD, team leader in Precision Cancer Medicine at The Institute of Cancer Research.

“This could allow doctors to pick out those patients with more aggressive disease and treat them accordingly. Ultimately, it could lead to development of new molecular diagnostic tests to diagnose patients by their particular type of bowel [colorectal] cancer, and give them the most effective treatments for that type.”

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