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Genetic Alterations and Checkpoint Expression: Mechanisms and Models for Drug Discovery

  • Shuai Ding
  • Siqi Li
  • Shujie Zhang
  • Yan LiEmail author
Chapter
  • 156 Downloads
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1248)

Abstract

In this chapter, we will sketch a story that begins with the breakdown of chromosome homeostasis and genomic stability. Genomic alterations may render tumor cells eternal life at the expense of immunogenicity. Although antitumor immunity can be primed through neoantigens or inflammatory signals, tumor cells have evolved countermeasures to evade immune surveillance and strike back by modulating immune checkpoint related pathways. At present, monoclonal antibody drugs targeting checkpoints like PD-1 and CTLA-4 have significantly prolonged the survival of a variety of cancer patients, and thus have marked a great achievement in the history of antitumor therapy. Nevertheless, this is not the end of the story. As the relationship between genomic alteration and checkpoint expression is being delineated though the advances of preclinical animal models and emerging technologies, novel checkpoint targets are on the way to be discovered.

Keywords

Genetic alteration Checkpoint inhibitor Oncogenic mutation Chromosomal aberration Preclinical mouse model 

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© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  1. 1.The State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolModel Animal Research Center of Nanjing UniversityNanjing, JiangsuChina

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