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- Title
The distinct clinical trajectory, metastatic sites, and immunobiology of microsatellite-instability-high cancers.
- Authors
Shuting Han; Aik Yong Chok; Yang Yao Peh, Daniel; Zhi-Ming Ho, Joshua; Kwong Wei Tan, Emile; Si-Lin Koo; Iain Bee-Huat Tan; Chin-Ann Ong, Johnny
- Abstract
Microsatellite-instability-high (MSI-H) cancers form a spectrum of solid organ tumors collectively known as Lynch Syndrome cancers, occurring not only in a subset of colorectal, endometrial, small bowel, gastric, pancreatic, and biliary tract cancers but also in prostate, breast, bladder, and thyroid cancers. Patients with Lynch Syndrome harbor germline mutations in mismatch repair genes, with a high degree of genomic instability, leading to somatic hypermutations and, therefore, oncogenesis and cancer progression. MSI-H cancers have unique clinicopathological characteristics compared to their microsatellitestable (MSS) counterparts, marked by a higher neoantigen load, immune cell infiltration, and a marked clinical response to immune checkpoint blockade. Patients with known Lynch Syndrome may be detected early through surveillance, but some patients present with disseminated metastatic disease. The treatment landscape of MSI-H cancers, especially colorectal cancers, has undergone a paradigm shift and remains to be defined, with immune checkpoint blockade coming to the forefront of treatment strategies in the stage IV setting. We summarize in this review the clinical features of MSI-H cancers with a specific interest in the pattern of spread or recurrence, disease trajectory, and treatment strategies. We also summarize the tumor-immune landscape and genomic profile of MSI-H cancers and potential novel therapeutic strategies.
- Subjects
BILIARY tract cancer; HEREDITARY nonpolyposis colorectal cancer; IMMUNOLOGY; IMMUNE checkpoint proteins; PROSTATE; COLORECTAL cancer; BREAST; DNA mismatch repair
- Publication
Frontiers in Genetics, 2022, Vol 13, p1
- ISSN
1664-8021
- Publication type
Article
- DOI
10.3389/fgene.2022.933475