Cytosolic double-stranded DNA (dsDNA) is frequently accumulated in cancer cells due to chromosomal instability or exogenous stimulation. Cyclic GMP-AMP synthase (cGAS) acts as a cytosolic DNA sensor, which is activated upon binding to dsDNA to synthesize the crucial second messenger 2’3’-cyclic GMP-AMP (2’3’-cGAMP) that in turn triggers stimulator of interferon genes (STING) signaling. The canonical role of cGAS-cGAMP-STING pathway is essential for innate immunity and viral defense. Recent emerging evidence indicates that 2’3’-cGAMP plays an important role in cancer progression via cell autonomous and non-autonomous mechanisms. Beyond its role as an intracellular messenger to activate STING signaling in tumor cells, 2’3’-cGAMP also serves as an immunotransmitter produced by cancer cells to modulate the functions of non-tumor cells especially immune cells in the tumor microenvironment by activating STING signaling. In this review, we summarize the synthesis, transmission, and degradation of 2’3’-cGAMP as well as the dual functions of 2’3’-cGAMP in a STING-dependent manner. Additionally, we discuss the potential therapeutic strategies that harness the cGAMP-mediated antitumor response for cancer therapy.

由于染色体不稳定或外源刺激，胞质双链 DNA (dsDNA) 经常在癌细胞中积累。环 GMP-AMP 合酶 (cGAS) 充当胞质 DNA 传感器，在与 dsDNA 结合后被激活，合成关键的第二信使 2'3'-环 GMP-AMP (2'3'-cGAMP)，进而触发刺激器干扰素基因 (STING) 信号传导。 cGAS-cGAMP-STING 通路的典型作用对于先天免疫和病毒防御至关重要。最近出现的证据表明，2'3'-cGAMP 通过细胞自主和非自主机制在癌症进展中发挥重要作用。除了作为细胞内信使激活肿瘤细胞中的 STING 信号传导外，2'3'-cGAMP 还可以作为癌细胞产生的免疫递质，通过激活 STING 信号传导来调节肿瘤微环境中非肿瘤细胞尤其是免疫细胞的功能。在这篇综述中，我们总结了 2'3'-cGAMP 的合成、传递和降解，以及 2'3'-cGAMP 以 STING 依赖方式的双重功能。此外，我们还讨论了利用 cGAMP 介导的抗肿瘤反应进行癌症治疗的潜在治疗策略。