Yu Le, Liu Pengda
Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biochemistry and Biophysics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biochemistry and Biophysics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Semin Cancer Biol. 2024 Nov;106-107:87-102. doi: 10.1016/j.semcancer.2024.08.007. Epub 2024 Aug 31.
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.
cGAS/STING信号通路是先天免疫系统的关键组成部分，在感知胞质DNA、调节细胞衰老以及促进肿瘤发生中发挥着重要作用。最近的进展为多种病理生理环境中调控该通路激活的分子机制、cGAS/STING信号在细胞衰老中的不可或缺作用及其在癌症发生和抑制中的背景依赖性作用带来了新的认识。本综述总结了与cGAS/STING信号通路生物学及其参与衰老和肿瘤发生相关的现有知识。我们进一步探讨了cGAS/STING靶向治疗的临床意义和治疗潜力，以及该领域面临的挑战。本综述聚焦于分子机制和新兴药理学靶点，强调了未来研究利用cGAS/STING通路治疗衰老相关疾病和癌症的治疗潜力的重要性。对cGAS/STING信号调控机制的深入理解，以及疾病中相关的失调情况，再加上新型cGAS/STING调节剂的开发，为创造新颖有效的治疗策略带来了巨大希望。这些进展可以应对当前的治疗挑战，并释放cGAS/STING在治疗衰老相关疾病和肿瘤发生方面的全部潜力。
