The cGAS/STING signaling pathway is a crucial component of the innate immune system, playing significant roles in sensing cytosolic DNA, regulating cellular senescence, and contributing to oncogenesis. Recent advances have shed new lights into the molecular mechanisms governing pathway activation in multiple pathophysiological settings, the indispensable roles of cGAS/STING signaling in cellular senescence, and its context-dependent roles in cancer development and suppression. This review summarizes current knowledge related to the biology of cGAS/STING signaling pathway and its participations into senescence and oncogenesis. We further explore the clinical implications and therapeutic potential for cGAS/STING targeted therapies, and faced challenges in the field. With a focus on molecular mechanisms and emerging pharmacological targets, this review underscores the importance of future studies to harness the therapeutic potential of the cGAS/STING pathway in treating senescence-related disorders and cancer. Advanced understanding of the regulatory mechanisms of cGAS/STING signaling, along with the associated deregulations in diseases, combined with the development of new classes of cGAS/STING modulators, hold great promises for creating novel and effective therapeutic strategies. These advancements could address current treatment challenges and unlock the full potential of cGAS/STING in treating senescence-related disorders and oncogenesis.
Keywords: Human disorders; Innate immunity; Oncogenesis; STING; Senescence; Treatment; cGAS.
Copyright © 2024 Elsevier Ltd. All rights reserved.