Microsatellite instability in gastric cancer: molecular bases, clinical perspectives, and new treatment approaches.
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Embargo End Date
ICR Authors
Authors
Ratti, M
Lampis, A
Hahne, JC
Passalacqua, R
Valeri, N
Lampis, A
Hahne, JC
Passalacqua, R
Valeri, N
Document Type
Journal Article
Date
2018-11-01
Date Accepted
2018-08-14
Abstract
Gastric cancer is one of the most aggressive malignancies, with limited treatment options in both locally advanced and metastatic setting, resulting in poor prognosis. Based on genomic characterization, stomach tumour has recently been described as a heterogeneous disease composed by different subtypes, each of them with peculiar molecular aspects and specific clinical behaviour. With an incidence of 22% among all western gastric tumour cases, stomach cancer with microsatellite instability was identified as one of these subgroups. Retrospective studies and limited prospective trials reported differences between gastric cancers with microsatellite stability and those with instability, mainly concerning clinical and pathological features, but also in regard to immunological microenvironment, correlation with prognostic value, and responses to treatment. In particular, gastric cancer with microsatellite instability constitutes a small but relevant subgroup associated with older age, female sex, distal stomach location, and lower number of lymph-node metastases. Emerging data attribute to microsatellite instability status a favourable prognostic meaning, whereas the poor outcomes reported after perioperative chemotherapy administration suggest a detrimental role of cytotoxic drugs in this gastric cancer subgroup. The strong immunogenicity and the widespread expression of immune-checkpoint ligands make microsatellite instability subtype more vulnerable to immunotherapeutic approach, e.g., with anti-PD-L1 and anti-CTLA4 antibodies. Since gastric cancer with microsatellite instability shows specific features and clinical behaviour not overlapping with microsatellite stable disease, microsatellite instability test might be suitable for inclusion in a diagnostic setting for all tumour stages to guarantee the most targeted and effective treatment to every patient.
Citation
Cellular and molecular life sciences : CMLS, 2018, 75 (22), pp. 4151 - 4162
Source Title
Publisher
SPRINGER BASEL AG
ISSN
1420-682X
eISSN
1420-9071
Collections
Research Team
Evolutionary Genomics & Modelling
Gastrointestinal Cancer Biology and Genomics
Gastrointestinal Cancer Biology and Genomics