Does colon tumour location play a role in metastasis and survival?
Despite being part of the same organ, right- and left-sided colorectal cancer show quite distinct disease characteristics. For example, right-sided tumours tend to show mutations in the DNA mismatch repair pathway (think: microsatellite instability (MSI)) while left-sided tumours tend to show mutations in KRAS, PIK3CA, and p53. The physical appearance of the tumours also differs, with right-sided tumours tending towards a more flattened appearance and left-sided tumours tending to resemble a polyp, or mushroom-like growth. Left-sided tumours tend to respond better to conventional 5-FU-(5-fluouracil)-based chemotherapies and targeted therapies such as anti-epidermal growth factor receptor (EGFR) therapies, while right-sided tumours do not respond well to conventional chemotherapies and instead show more promising response to immunotherapies1.
Recent findings published in Cancer Letters found that patient with right-sided colorectal tumours that spread to the liver had worse survival rates than those with left-sided tumours that had also metastasized to the liver. Left- and right-sided tumours have demonstrated biological differences which may explain the variations that are observed in the clinical behaviour of these two tumour types, especially in the metastatic setting.
Frozen liver metastasis samples from patients with right- and left-sided colon cancer were examined using laboratory analytical techniques (RNA sequencing and liquid chromatography mass spectrometry). The researchers found that colon cancer cells functioned differently and produced different cellular by-products (increase reactive oxygen species metabolites, bile acids in the right-sided samples; more carnitines (indicators of fatty acid oxidation) were found in left-sided samples) in right- and left-sided colon tumours, which they suggest may be relevant to the clinical differences that are seen in how the tumour behaves in right- and left-sided colon cancer liver metastasis.
The findings demonstrate that colorectal cancer liver metastases that original from different locations in the colon have distinct characteristics and behaviours. This understanding will help researchers to tailor treatment strategies and improve outcomes for patients with liver metastases, regardless of the primary tumour’s sidedness.