論文

査読有り 筆頭著者
2020年1月

Microsatellite instability and immune checkpoint inhibitors: toward precision medicine against gastrointestinal and hepatobiliary cancers.

Journal of gastroenterology
  • Yuji Eso
  • ,
  • Takahiro Shimizu
  • ,
  • Haruhiko Takeda
  • ,
  • Atsushi Takai
  • ,
  • Hiroyuki Marusawa

55
1
開始ページ
15
終了ページ
26
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s00535-019-01620-7

Recent innovations in the next-generation sequencing technologies have unveiled that the accumulation of genetic alterations results in the transformation of normal cells into cancer cells. Accurate and timely repair of DNA is, therefore, essential for maintaining genetic stability. Among various DNA repair pathways, the mismatch repair (MMR) pathway plays a pivotal role. MMR deficiency leads to a molecular feature of microsatellite instability (MSI) and predisposes to cancer. Recent studies revealed that MSI-high (MSI-H) or mismatch repair-deficient (dMMR) tumors, regardless of their primary site, have a promising response to immune checkpoint inhibitors (ICIs), leading to the approval of the anti-programmed cell death protein 1 monoclonal antibody pembrolizumab for the treatment of advanced or recurrent MSI-H/dMMR solid tumors that continue to progress after conventional chemotherapies. This new indication marks a paradigm shift in the therapeutic strategy of cancers; however, when considering the optimum indication for ICIs and their safe and effective usage, it is important for clinicians to understand the genetic and immunologic features of each tumor. In this review, we describe the molecular basis of the MMR pathway, diagnostics of MSI status, and the clinical importance of MSI status and the tumor mutation burden in developing therapeutic strategies against gastrointestinal and hepatobiliary malignancies.

リンク情報
DOI
https://doi.org/10.1007/s00535-019-01620-7
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31494725
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942585
ID情報
  • DOI : 10.1007/s00535-019-01620-7
  • ISSN : 0944-1174
  • PubMed ID : 31494725
  • PubMed Central 記事ID : PMC6942585

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