Research Progress on the Role of Natural Active Substances in Regulating Adenosine Pathway in Tumor Therapy

The incidence of cancer is increasing year by year, becoming a major public health problem worldwide. Tumor is a complex ecosystem, and tumor cells can escape recognition and killing by the immune system through a variety of mechanisms. Among them, adenosine (ADO) stands out as a highly immunosuppressive compound derived from the degradation of adenosine triphosphate (ATP) released by dying or stressed cells. ADO is prevalent in the tumor microenvironment of most solid tumors, promoting tumor cell proliferation, migration, invasion, angiogenesis, and chemotherapy resistance. Adenosine receptors (ARs) on tumor and immune cells, when activated by ADO, inhibit tumor antigen presentation and immune cell activation, suppressing tumor immunity. Targeting the adenosine pathway is thus a key focus in tumor immunotherapy. Natural compounds like alkaloids, flavonoids, and polyphenols show promise in modulating adenosine pathways by interfering with its production, transport, or receptor signaling, potentially reversing tumor immunosuppression. This paper reviews adenosine's metabolic pathways and its role in the tumor microenvironment, exploring how natural substances can regulate these pathways, offering new insights for cancer prevention and treatment.