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Published on: March 14, 2019
State of the art: Targeting microsatellite instability in gastrointestinal cancers
Justin Mencel1, Anneke Alves1, Vasileios Angelis1
1Gastrointestinal and Lymphoma Unit, Royal Marsden NHS Foundation, London, United Kingdom.
Abstract:
DNA mismatch repair (MMR) deficiency and the associated microsatellite instability (MSI) phenotype has become a subject of enormous interest in recent years due to the demonstrated efficacy of immune checkpoint inhibitors (ICI) in advanced tumours. Assessing MSI in patients with gastrointestinal tract (GI) cancers is useful to exclude Lynch syndrome, but also to predict benefit for ICI. Following review of the relevant literature, this review article aims to outline the clinicopathologic spectrum of MSI and mismatch repair deficiency (dMMR) in the GI tract, hepatobiliary system and pancreas and discuss the therapeutic consideration in this disease.
Insights
Microsatellite instability (MSI) and DNA mismatch repair (MMR) deficiency are crucial in advanced cancers. Assessing MSI in gastrointestinal cancers predicts immune checkpoint inhibitor (ICI) benefit and aids Lynch syndrome diagnosis.
Area of Science:
- Oncology
- Gastroenterology
- Immunotherapy
Background:
- DNA mismatch repair (MMR) deficiency leads to microsatellite instability (MSI) phenotype.
- This phenotype is increasingly recognized for its role in advanced tumors.
- Immune checkpoint inhibitors (ICIs) show significant efficacy in MSI-high tumors.
Purpose of the Study:
- To review the clinicopathologic spectrum of MSI and MMR deficiency (dMMR).
- To cover MSI/dMMR in the gastrointestinal tract, hepatobiliary system, and pancreas.
- To discuss therapeutic considerations for MSI/dMMR in these cancers.
Main Methods:
- Literature review of relevant studies.
- Analysis of clinicopathologic features.
- Discussion of therapeutic strategies.
Main Results:
- MSI/dMMR has a distinct clinicopathologic spectrum across GI, hepatobiliary, and pancreatic cancers.
- MSI assessment in GI cancers is vital for Lynch syndrome exclusion.
- MSI status predicts response to immune checkpoint inhibitors.
Conclusions:
- MSI/dMMR is a critical biomarker in GI, hepatobiliary, and pancreatic cancers.
- Understanding MSI/dMMR aids in patient selection for immunotherapy.
- Further research into therapeutic strategies for MSI/dMMR cancers is warranted.
