Controversies and management of deficient mismatch repair gastrointestinal cancers in the neoadjuvant setting

Abstract

High microsatellite instability (MSI-H)/deficient mismatch repair (dMMR) phenotype is a distinct molecular signature across gastrointestinal cancers characterized by high tumor mutational burden and high neoantigen load. Tumors harboring dMMR are highly immunogenic and heavily infiltrated by immune cells; consequently, they are uniquely vulnerable to therapeutic strategies enhancing immune antitumor response such as checkpoint inhibitors. The MSI-H/dMMR phenotype arose as a powerful predictor of response to immune checkpoint inhibitors with evidence supporting significantly improved outcomes in the metastatic setting. On the other hand, the genomic instability characteristic of MSI-H/dMMR tumors appears to be associated with decreased sensitivity to chemotherapy, and the benefits of standard adjuvant or neoadjuvant chemotherapy approaches in this subtype are being increasingly questioned. Here, we review the prognostic and predictive impact of MMR status in localized gastric and colorectal cancers, and highlight the emerging clinical data incorporating checkpoint inhibitors in the neoadjuvant setting.

DNA Mismatch Repair Assessment in Gastric and Colon Cancers Using Stochastic Microdisks

“…Discussions of the role of mismatch repair in colorectal cancer and gastric cancer were concluded [18–20] that there is a high need for reliable screening methods able to determine simultaneously MLH1, MSH2, MSH6, PMS2, and KRAS in biological samples. Therefore, this paper proposed two stochastic microdisks able to determine simultaneously MLH1, MSH2, MSH6, PMS2, and KRAS in whole blood, saliva, urine, and tumoral tissues.…”