cGAS‐STING signaling in cancer: Regulation and therapeutic targeting

Abstract

Immunotherapy has revolutionized antitumor therapy. Since the discovery of stimulators of interferon genes (STING), efforts have been made to elucidate their mechanisms and physiological functions and explore the potential of STING as a therapeutic target in immune‐related diseases and malignant tumors. In recent years, STING agonists have become a popular research topic. Activation of the cyclic GMP–AMP synthase (cGAS)‐STING pathway produces large amounts of type I interferons, which play key roles in activating innate and acquired immune responses. The cGAS‐STING pathway influences almost all aspects of tumorigenesis and has great antitumor potential. In addition, the activation of the cGAS‐STING pathway is associated with tumor regression, prolonged survival of patients with cancer, and enhanced immunotherapy. Given the positive role of STING in antitumor immunity, the development of STING‐targeted drugs is important. In this review, we summarize the activation and potential mechanisms of the cGAS‐STING pathway, discuss the association of the cGAS‐STING pathway with tumors and autoimmune diseases, and highlight research progress, clinical applications, and combination drug strategies for STING agonists.

The hidden architects of glioblastoma multiforme: Glioma stem cells

“…Analogous to the niche of NSCs, GSCs also orchestrate several regulatory pathways, viz. the BMP, Notch, Hedgehog, NF‐ĸB, and Wnt signaling 9 . Apart from the signalling cascades, several other factors like VEGF and HIF are also known to structure the fate of GSCs in GBM, hence provide selective advantages to maintain tumor stemness and growth.…”

“…These signatures not only distinguish GSCs from nonstem tumor cells but also contribute to their resistance to conventional therapies. For instance, dysregulation of key signaling pathways, including the Notch, Hedgehog, and Wnt pathways, has been implicated in maintaining the stem cell phenotype of GSCs 6–9 . Furthermore, GSCs contribute to intratumoral heterogeneity by generating diverse cell lineages within the tumor mass.…”