The cGAS/STING Pathway: A Novel Target for Cancer Therapy

Abstract

As a DNA receptor, cyclic GMP-AMP synthase (cGAS) plays a crucial role in the immune system by recognizing abnormal DNA in the cytoplasm and activating the stimulator of interferon genes (STING) signaling pathway. This signaling cascade reaction leads to an immune response produced by type I interferon and other immune mediators. Recent advances in research have enhanced our current understanding of the potential role of the cGAS/STING pathway in anticancer therapy; however, in some cases, chronic STING activation may promote tumorigenesis. The present review article discusses the biological mechanisms of the cGAS/STING pathway, its dichotomous role in tumors, and the latest advances with respect to STING agonists and antagonists.

Bibliometric and Visualized Analysis of the Current Status on STING Signaling Pathway and Cancer

“…Novel immunotherapy are transforming the treatment of cancer over the past two decades [ 36 , 37 ]. The cGAS-STING signaling pathway has a dichotomous role in cancer, with both autonomous and involuntary antitumor effects in tumor cells [ 38 ]. Song et al [ 39 ] demonstrated that STING protein expression was remarkably decreased in gastric cancer can promote the progression of tumor, promote colony formation, viability, migration, and invasion of gastric cancer cells and STING can be regarded as a potential prognostic marker for gastric cancer patients.…”

Activation of Stimulation of Interferon Genes (STING) Signal and Cancer Immunotherapy

“…The activation of the cGAS-STING pathway may induce various cytokines and stimulate adaptive immunity. When STING agonists are combined with other cancer therapies, it might achieve positive feedback, improve the tumor microenvironment, and lead to a sustained anti-tumor effect [ 97 ].…”

Ligands stimulating antitumour immunity as the next G-quadruplex challenge

“…STING may therefore affect genome stability, regulating the DNA damage response by favouring the formation of the non-homologous end joining (NHEJ)-initiation complex at DNA damage sites, promoting breast cancer cell survival and resistance to genotoxic stress [ 141 ]. The role of STING in cancer progression and treatment is therefore more complex as it exhibits both tumour-suppressive and tumour-promoting effects [ 142 , 143 ]. Overall published data show that, in addition to short-term advantages in promoting immune-surveillance, long-term effects of STING pathways can promote cancer progression through chronic inflammation and enhanced immune-suppressive microenvironment.…”