Clinical characteristics and responses to chemotherapy and immune checkpoint inhibitor treatment for microsatellite instability gastric cancer.

ABSTRACT

During the process of DNA replication, insertions or deletions of repeat sequences easily occur in microsatellites due to DNA polymerase slippage in instances of defective mismatch repair; this phenomenon is known as microsatellite instability. Based on genetic profiling, microsatellite instability gastric cancer is regarded as a separate subtype of gastric cancer that is associated with old age, the female sex, a distal gastric location, and a lower number of lymph node metastases. According to numerous retrospective studies, microsatellite instability is a favourable predictive marker for prognosis. However, during the perioperative period, gastric cancer patients with microsatellite instability after chemotherapy often exhibit a poor and unfavourable prognosis. This result still remains controversial. The efficacy of adjuvant chemotherapy in microsatellite instability-high tumours ranges from detrimental to beneficial effects. Due to the widespread expression of immune checkpoint molecules (such as programmed death-1 and programmed death-ligand 1) in tumours with microsatellite instability, immune checkpoint inhibitors have been utilized to treat microsatellite instability gastric cancer and tremendously improve the efficacy of treatment and survival of microsatellite instability patients. In this review, we attempt to outline the definitions of microsatellites and microsatellite instability, the methods used to screen for microsatellite instability, the clinical characteristics of microsatellite instability gastric cancer, and its responses to chemotherapy and immune checkpoint inhibitor treatment. Overall, determining the status of microsatellites is essential before developing a tailored treatment strategy for patients with microsatellite instability gastric cancer.