4.7 Review

cGAS-STING pathway in cancer biotherapy

Journal

MOLECULAR CANCER
Volume 19, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12943-020-01247-w

Keywords

cGAS-STING pathway; Cancer biotherapy; Interferon; Cyclic dinucleotide; Agonist; Delivery system; Clinical trials

Funding

  1. National Natural Science Foundation Regional Innovation and Development [U19A2003]
  2. National Major Scientific and Technological Special Project for Significant New Drugs Development [2018ZX09733001]
  3. Excellent Youth Foundation of Sichuan Scientific Committee Grant in China [2019JDJQ008]
  4. Development Program of China [2016YFA0201402]

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The activation of the cGAS-STING pathway has tremendous potential to improve anti-tumor immunity by generating type I interferons. In recent decades, we have witnessed that producing dsDNA upon various stimuli is an initiative factor, triggering the cGAS-SING pathway for a defensive host. The understanding of both intracellular cascade reaction and the changes of molecular components gains insight into type I IFNs and adaptive immunity. Based on the immunological study, the STING-cGAS pathway is coupled to cancer biotherapy. The most challenging problem is the limited therapeutic effect. Therefore, people view 5, 6-dimethylxanthenone-4-acetic acid, cyclic dinucleotides and various derivative as cGAS-STING pathway agonists. Even so, these agonists have flaws in decreasing biotherapeutic efficacy. Subsequently, we exploited agonist delivery systems (nanocarriers, microparticles and hydrogels). The article will discuss the activation of the cGAS-STING pathway and underlying mechanisms, with an introduction of cGAS-STING agonists, related clinical trials and agonist delivery systems.

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