The cGAS–cGAMP–STING pathway connects DNA damage to inflammation, senescence, and cancer. This pathway detects cytoplasmic DNA, which is a danger-associated molecular pattern (DAMP), and triggers innate immune responses. cGAS, a DNA sensor, produces the second messenger cGAMP, which activates the adaptor protein STING. STING then activates transcription factors such as IRF3 and NF-κB, leading to the production of type I IFNs and other cytokines. This pathway is crucial for linking DNA damage to inflammatory responses, cellular senescence, and cancer. Genomic instability, a major driver of cancer and age-related diseases, can lead to DNA damage, which activates the cGAS–cGAMP–STING pathway. This pathway is involved in the induction of cytokines and inflammatory responses, as well as in the regulation of cellular senescence and cancer. DNA damage can lead to the accumulation of cytoplasmic DNA, which is sensed by cGAS and activates the pathway. This process is also influenced by factors such as the MUS81 endonuclease and the Trex1 exonuclease. The cGAS–cGAMP–STING pathway is also implicated in autoinflammatory diseases, such as Aicardi-Goutières syndrome (AGS) and Ataxia-Telangiectasia (A-T). Mutations in genes involved in DNA metabolism, such as TREX1, RNASEH2, and SAMHD1, can lead to chronic IFN signaling and autoinflammatory phenotypes. The pathway is also involved in the regulation of cellular senescence, where it contributes to the expression of senescence markers and the production of cytokines that reinforce senescence signaling. In cancer, the cGAS–cGAMP–STING pathway plays a dual role. On one hand, it promotes antitumor immunity by activating immune responses and inducing cellular senescence in tumor cells. On the other hand, it can contribute to inflammation-driven carcinogenesis and metastasis. The pathway is also involved in shaping the tumor microenvironment and can lead to cell death, providing resistance to tumorigenesis. However, the activation of the pathway can also exacerbate certain cancers by promoting inflammatory responses. The cGAS–cGAMP–STING pathway is a promising target for cancer therapy, as it can be used to enhance antitumor immunity and promote cellular senescence. However, the activation of this pathway must be carefully controlled to avoid excessive inflammation and autoimmune responses. Research into the mechanisms of cGAS activation and the regulation of the pathway is ongoing, with the goal of developing targeted therapies that can harness the beneficial effects of the pathway while minimizing its harmful effects.The cGAS–cGAMP–STING pathway connects DNA damage to inflammation, senescence, and cancer. This pathway detects cytoplasmic DNA, which is a danger-associated molecular pattern (DAMP), and triggers innate immune responses. cGAS, a DNA sensor, produces the second messenger cGAMP, which activates the adaptor protein STING. STING then activates transcription factors such as IRF3 and NF-κB, leading to the production of type I IFNs and other cytokines. This pathway is crucial for linking DNA damage to inflammatory responses, cellular senescence, and cancer. Genomic instability, a major driver of cancer and age-related diseases, can lead to DNA damage, which activates the cGAS–cGAMP–STING pathway. This pathway is involved in the induction of cytokines and inflammatory responses, as well as in the regulation of cellular senescence and cancer. DNA damage can lead to the accumulation of cytoplasmic DNA, which is sensed by cGAS and activates the pathway. This process is also influenced by factors such as the MUS81 endonuclease and the Trex1 exonuclease. The cGAS–cGAMP–STING pathway is also implicated in autoinflammatory diseases, such as Aicardi-Goutières syndrome (AGS) and Ataxia-Telangiectasia (A-T). Mutations in genes involved in DNA metabolism, such as TREX1, RNASEH2, and SAMHD1, can lead to chronic IFN signaling and autoinflammatory phenotypes. The pathway is also involved in the regulation of cellular senescence, where it contributes to the expression of senescence markers and the production of cytokines that reinforce senescence signaling. In cancer, the cGAS–cGAMP–STING pathway plays a dual role. On one hand, it promotes antitumor immunity by activating immune responses and inducing cellular senescence in tumor cells. On the other hand, it can contribute to inflammation-driven carcinogenesis and metastasis. The pathway is also involved in shaping the tumor microenvironment and can lead to cell death, providing resistance to tumorigenesis. However, the activation of the pathway can also exacerbate certain cancers by promoting inflammatory responses. The cGAS–cGAMP–STING pathway is a promising target for cancer therapy, as it can be used to enhance antitumor immunity and promote cellular senescence. However, the activation of this pathway must be carefully controlled to avoid excessive inflammation and autoimmune responses. Research into the mechanisms of cGAS activation and the regulation of the pathway is ongoing, with the goal of developing targeted therapies that can harness the beneficial effects of the pathway while minimizing its harmful effects.