Pharmacological Modulation of the STING Pathway for Cancer Immunotherapy

Trends Mol Med. 2019 May;25(5):412-427. doi: 10.1016/j.molmed.2019.02.007. Epub 2019 Mar 15.


The advent of immunotherapy in recent years has shown the potential to revolutionize the treatment of cancer. Unleashing antitumor T cell responses via immune checkpoint blockade has led to remarkable responses in previously untreatable tumors. The master regulator of interferon-mediated antiviral responses - stimulator of interferon genes (STING) - has now emerged as a critical mediator of innate immune sensing of cancer, and is a promising target for local immunostimulation, promoting intratumoral inflammation, and facilitating antitumor T cell responses. Pharmacological activation of the STING pathway can lead to T cell-mediated tumor regression in preclinical tumor models, and novel STING activating small molecules are now being tested in clinical trials. Here we will introduce the STING pathway and review the current state of drug development.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Immunological / chemistry
  • Antineoplastic Agents, Immunological / pharmacology*
  • Antineoplastic Agents, Immunological / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor
  • Humans
  • Immunomodulation / drug effects*
  • Immunotherapy
  • Membrane Proteins / agonists
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / etiology*
  • Neoplasms / metabolism*
  • Nucleotidyltransferases / chemistry
  • Nucleotidyltransferases / metabolism
  • Protein Binding
  • Signal Transduction / drug effects*
  • Structure-Activity Relationship


  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor
  • Membrane Proteins
  • STING1 protein, human
  • Nucleotidyltransferases
  • cGAS protein, human