Cyclic adenosine monophosphate (cAMP) signaling plays a critical role in cancer progression and the tumor microenvironment (TME). cAMP acts through downstream effectors such as cAMP-dependent protein kinase (PKA) and exchange protein activated by cAMP (EPAC), which can either promote or inhibit cancer cell growth depending on the context. Tumor-associated stromal cells, including cancer-associated fibroblasts (CAFs) and immune cells, can modulate cAMP levels, influencing tumor progression. Targeting cAMP signaling in the TME has shown therapeutic potential in cancer, with small-molecule inhibitors of adenylate cyclase and PKA, as well as cAMP-elevating agents like forskolin, demonstrating anti-tumor effects. cAMP signaling is involved in various physiological and pathological processes, including cell proliferation, survival, and immune evasion. The dual role of cAMP in oncogenesis is context-dependent, with both agonists and antagonists of cAMP signaling being explored for cancer treatment. cAMP signaling pathways involve multiple proteins, including PKA, EPAC, and ion channels, and are regulated by various enzymes such as phosphodiesterases (PDEs). cAMP signaling is also involved in immune cell function, with regulatory T cells (Tregs) playing a key role in immune regulation through cAMP production. The complex interplay between cAMP signaling and the TME is crucial for understanding cancer progression and developing effective therapies.Cyclic adenosine monophosphate (cAMP) signaling plays a critical role in cancer progression and the tumor microenvironment (TME). cAMP acts through downstream effectors such as cAMP-dependent protein kinase (PKA) and exchange protein activated by cAMP (EPAC), which can either promote or inhibit cancer cell growth depending on the context. Tumor-associated stromal cells, including cancer-associated fibroblasts (CAFs) and immune cells, can modulate cAMP levels, influencing tumor progression. Targeting cAMP signaling in the TME has shown therapeutic potential in cancer, with small-molecule inhibitors of adenylate cyclase and PKA, as well as cAMP-elevating agents like forskolin, demonstrating anti-tumor effects. cAMP signaling is involved in various physiological and pathological processes, including cell proliferation, survival, and immune evasion. The dual role of cAMP in oncogenesis is context-dependent, with both agonists and antagonists of cAMP signaling being explored for cancer treatment. cAMP signaling pathways involve multiple proteins, including PKA, EPAC, and ion channels, and are regulated by various enzymes such as phosphodiesterases (PDEs). cAMP signaling is also involved in immune cell function, with regulatory T cells (Tregs) playing a key role in immune regulation through cAMP production. The complex interplay between cAMP signaling and the TME is crucial for understanding cancer progression and developing effective therapies.