cGAS-STING at the crossroads in cancer therapy

Abstract

DNA is highly immunogenic, both exogenous and endogenous DNA can activate the pathogen-associated molecular pattern (PAMP) and danger-associated molecular pattern (DAMP), respectively, and hence activate the evolutionarily conserved cGAS-STING pathway for inflammatory responses. The cGAS-STING signaling pathway plays a very important role in the pathogenesis and progression of neoplastic diseases. For cancer therapy, there are some discrepancies on whether cGAS-STING should be inhibited or activated. Deregulated cGAS-STING signaling pathway might be the origin and pathogenesis of tumor, understanding and modulating cGAS-STING signaling holds great promise for cancer therapy. In this review article, we discuss the molecular mechanisms underlying cGAS-STING deregulation, highlighting the tumor inhibiting and promoting roles and challenges with cGAS-STING agonists in the context of cancer therapies.

Keywords: Agonist; Antagonist; CGAS; Innate immunity; STING; Tumorigenesis.