研究者情報

ワタナベ　ヨシユキ   WATANABE YOSHIYUKI   渡邊嘉行    所属   医学部医学科 消化器内科    職種   非常勤講師
論文種別	総説・解説
言語種別	英語
査読の有無	査読あり
表題	Microsatellite instability: A 2024 update
掲載誌名	正式名：Cancer Science 略　 称：Cancer Sci. ISSNコード：1347-9032/1349-7006
掲載区分	国内
出版社名	Wiley
巻・号・頁	DOI-10.1111/cas.16160頁
著者・共著者	Yamamoto Hiroyuki, Watanabe Yoshiyuki, Arai, Hiroyuki Umemoto Kumiko, Tateishi Keisuke, Sunakawa Yu
発行年月	2024/03
概要	Deficient mismatch repair (dMMR) results in microsatellite instability (MSI), a pronounced mutator phenotype. High-frequency MSI (MSI-H)/dMMR is gaining increasing interest as a biomarker for advanced cancer patients to determine their eligibility for immune checkpoint inhibitors (ICIs). Various methods based on next-generation sequencing (NGS) have been developed to assess the MSI status. Comprehensive genomic profiling (CGP) testing can precisely ascertain the MSI status as well as genomic alterations in a single NGS test. The MSI status can be also ascertained through the liquid biopsy-based CGP assays. MSI-H has thus been identified in various classes of tumors, resulting in a greater adoption of immunotherapy, which is hypothesized to be effective against malignancies that possess a substantial number of mutations and/or neoantigens. NGS-based studies have also characterized MSI-driven carcinogenesis, including significant rates of fusion kinases in colorectal cancers (CRCs) with MSI-H that are targets for therapeutic kinase inhibitors, particularly in MLH1-methylated CRCs with wild-type KRAS/BRAF. NTRK fusion is linked to the colorectal serrated neoplasia pathway. Recent advances in investigations of MSI-H malignancies have resulted in the development of novel diagnostic or therapeutic techniques, such as a synthetic lethal therapy that targets the Werner gene. DNA sensing in cancer cells is required for antitumor immunity induced by dMMR, opening up novel avenues and biomarkers for immunotherapy. Therefore, clinical relevance exists for analyses of MSI and MSI-H-associated genomic alterations in malignancy. In this article, we provide an update on MSI-driven carcinogenesis, with an emphasis on unique landscapes of diagnostic and immunotherapeutic strategies.
DOI	10.1111/cas.16160
PMID	38528657