Abstract
Colorectal cancer is one of the most common tumours in the world, with microsatellite instability having an important role in the development of these tumours. Microsatellite instability is responsible for the worse response of tumours to chemotherapy, while also having a role in the better prognosis associated with these tumours. This relates to the higher immune infiltration that results from the high neoantigen load of microsatellite unstable tumours. This highly responsive immune microenvironment seen in microsatellite unstable colorectal cancer makes these tumours great candidates for therapies targeting the immune system, such as immune checkpoint inhibitors. The PD-1/PD-L1 axis is upregulated in colorectal cancer with microsatellite instability, making the blockade of this axis a good therapy alternative for these patients.
Highlights
Colorectal cancer is one of the most common tumours in the world in both men and women, while chemotherapy and surgery remain the standard of care for these patients [1] Microsatellite instability is responsible for about 15% of these tumours, with 5% of all Colorectal Cancer (CRC) being associated with hereditary Microsatellite Instability (MSI) [2]
[1] Microsatellite instability is responsible for about 15% of these tumours, with 5% of all CRC being associated with hereditary MSI [2]
While MSI is typically associated with a better prognosis and longer Overall Survival (OS), it is known to be a predictor of poorer response to chemotherapy with 5-FU derivates [3], fluoropyrimidines, platinum compounds and methylating agents
Summary
CRC is one of the most common tumours in the world, with MSI having an important role in both the development of these tumours and their response to the available therapies, making the response to chemotherapy worse than in other CRC subtypes. MSI is responsible for a characteristic tumour microenvironment which favours these tumours’ response to immunotherapy, mainly through the blockade of the PD-1/PD-L1 axis, such as the PD-1 blocker pembrolizumab. Clinical trials show the good response rates and improvement in OS of patients with MSI CRC treated with pembrolizumab, making this the rationale for the implementation of this antibody in the treatment of CRC with MSI
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