The aryl hydrocarbon receptor (AhR) plays a crucial role in maintaining homeostasis in barrier organs such as the skin, lungs, and gut, which are essential for protecting the body from environmental stressors. AhR is a ligand-dependent transcription factor initially discovered as a receptor for environmental carcinogens like polycyclic aromatic hydrocarbons (PAHs). However, its role in carcinogenesis is complex and can be both pro- and anti-tumor. AhR activation can promote carcinogenesis by increasing DNA damage and mutations, but it can also act as a tumor suppressor by regulating immune responses and maintaining intestinal homeostasis. The AhR pathway is activated by various ligands, including environmental toxins and endogenous metabolites, and its function varies depending on the type of cancer and the concentration of ligands. Genetic studies have shown that AhR mutations are specific to bladder cancer, while AhR expression is altered in various types of cancer, including breast, lung, and colorectal cancer. AhR has been linked to both the promotion and inhibition of carcinogenesis, depending on the context. For example, AhR activation by UV radiation can enhance skin carcinogenesis by impairing DNA repair and promoting immunosuppression, while AhR antagonists have shown preclinical efficacy in preventing carcinogenesis. In the lungs, AhR activation by PAHs can promote lung cancer by inducing DNA damage and promoting inflammation. However, AhR can also inhibit cigarette smoke-induced acute lung inflammation and facilitate the degradation of pro-inflammatory cytokines. In the gut, AhR plays a role in maintaining intestinal homeostasis and immune regulation. AhR deletion enhances colitis-associated colorectal tumors, while natural AhR ligands like indole-3-carbinol (I3C) reduce tumor burden. Microbiota-derived short-chain fatty acids, such as butyrate, can influence AhR activity and potentially affect colorectal cancer development. Immunological studies have shown that AhR activation can enhance antitumor immunity by promoting the activity of natural killer (NK) cells and other immune cells. However, AhR can also facilitate tumor immune escape by promoting the production of regulatory T (Treg) cells and other immunosuppressive cells. AhR agonists and antagonists have shown preclinical efficacy in cancer chemoprevention, but specific ligands may drive or suppress carcinogenesis, making the selection of appropriate modulators crucial. In conclusion, AhR plays a complex role in carcinogenesis, and further research is needed to fully understand its mechanisms and potential as a target for cancer prevention and treatment.The aryl hydrocarbon receptor (AhR) plays a crucial role in maintaining homeostasis in barrier organs such as the skin, lungs, and gut, which are essential for protecting the body from environmental stressors. AhR is a ligand-dependent transcription factor initially discovered as a receptor for environmental carcinogens like polycyclic aromatic hydrocarbons (PAHs). However, its role in carcinogenesis is complex and can be both pro- and anti-tumor. AhR activation can promote carcinogenesis by increasing DNA damage and mutations, but it can also act as a tumor suppressor by regulating immune responses and maintaining intestinal homeostasis. The AhR pathway is activated by various ligands, including environmental toxins and endogenous metabolites, and its function varies depending on the type of cancer and the concentration of ligands. Genetic studies have shown that AhR mutations are specific to bladder cancer, while AhR expression is altered in various types of cancer, including breast, lung, and colorectal cancer. AhR has been linked to both the promotion and inhibition of carcinogenesis, depending on the context. For example, AhR activation by UV radiation can enhance skin carcinogenesis by impairing DNA repair and promoting immunosuppression, while AhR antagonists have shown preclinical efficacy in preventing carcinogenesis. In the lungs, AhR activation by PAHs can promote lung cancer by inducing DNA damage and promoting inflammation. However, AhR can also inhibit cigarette smoke-induced acute lung inflammation and facilitate the degradation of pro-inflammatory cytokines. In the gut, AhR plays a role in maintaining intestinal homeostasis and immune regulation. AhR deletion enhances colitis-associated colorectal tumors, while natural AhR ligands like indole-3-carbinol (I3C) reduce tumor burden. Microbiota-derived short-chain fatty acids, such as butyrate, can influence AhR activity and potentially affect colorectal cancer development. Immunological studies have shown that AhR activation can enhance antitumor immunity by promoting the activity of natural killer (NK) cells and other immune cells. However, AhR can also facilitate tumor immune escape by promoting the production of regulatory T (Treg) cells and other immunosuppressive cells. AhR agonists and antagonists have shown preclinical efficacy in cancer chemoprevention, but specific ligands may drive or suppress carcinogenesis, making the selection of appropriate modulators crucial. In conclusion, AhR plays a complex role in carcinogenesis, and further research is needed to fully understand its mechanisms and potential as a target for cancer prevention and treatment.