Microsatellite instability in cancer: a novel landscape for diagnostic and therapeutic approach View Full Text


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Article Info

DATE

2020-07-06

AUTHORS

Hiroyuki Yamamoto, Yoshiyuki Watanabe, Tadateru Maehata, Kohzoh Imai, Fumio Itoh

ABSTRACT

Defective DNA mismatch repair creates a strong mutator phenotype, recognized as microsatellite instability (MSI). Various next-generation sequencing-based methods for evaluating cancer MSI status have been established, and NGS-based studies have thoroughly described MSI-driven tumorigenesis. Accordingly, high-frequency MSI (MSI-H) has been detected in 81 tumor types, including those in which MSI was previously underrated. The findings have increased the use of immunotherapy, which is assumed to be efficient in tumors having a high mutation burden and/or neoantigen load. In MSI tumorigenesis, positively and negatively selected driver gene mutations have been characterized in colorectal cancers. Recent advancements in genome-wide studies of MSI-H cancers have developed novel diagnostic and therapeutic approaches, including CXCR2 inhibitor, a synthetic lethal therapy targeting the Werner gene and inhibition of nonsense-mediated mRNA decay. MSI is a predictive marker for chemotherapy as well as immunotherapy. Thus, analyses of MSI status and MSI-related alterations in cancers are clinically relevant. We present an update on MSI-driven tumorigenesis, focusing on a novel landscape of diagnostic and therapeutic approaches. More... »

PAGES

3349-3357

References to SciGraph publications

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  • 2018-09-19. Targeting nonsense-mediated mRNA decay in colorectal cancers with microsatellite instability in ONCOGENESIS
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  • 2009-06-07. A UPF3-mediated regulatory switch that maintains RNA surveillance in NATURE STRUCTURAL & MOLECULAR BIOLOGY
  • 2014-09-12. Oral medicine: Amlexanox in BRITISH DENTAL JOURNAL
  • 2007-12-14. WRN promoter methylation possibly connects mucinous differentiation, microsatellite instability and CpG island methylator phenotype in colorectal cancer in MODERN PATHOLOGY
  • 2019-04-10. Prioritization of cancer therapeutic targets using CRISPR–Cas9 screens in NATURE
  • 2019-03-18. Immunotherapy in colorectal cancer: rationale, challenges and potential in NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
  • 2019-02-12. The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy in NATURE REVIEWS CANCER
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  • 2019-09-07. Microsatellite instability and immune checkpoint inhibitors: toward precision medicine against gastrointestinal and hepatobiliary cancers in JOURNAL OF GASTROENTEROLOGY
  • 2019-04-10. WRN helicase is a synthetic lethal target in microsatellite unstable cancers in NATURE
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    URI

    http://scigraph.springernature.com/pub.10.1007/s00204-020-02833-z

    DOI

    http://dx.doi.org/10.1007/s00204-020-02833-z

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1129027912

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/32632538


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