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Nowadays, tobacco smoking is the cause of approximately 5-6 million deaths per year.It is the major etiologic factor associated with lung cancer.Nicotine, the addictive component of tobacco, and its derived carcinogenic nitrosamines (i.e.NNK) contribute to lung cancer development and progression through the activation of nicotinic acetylcholine receptors (nAChR), specifically of the homomeric α7 sub-type.nAChR are ligand-gated ion channels, expressed in both normal and lung cancer cells, which mediate the proliferative, pro-survival, neo-angiogenic and metastatic effects of nicotine and its nitrosamine derivatives.The upregulation of cα7-nAChR by nicotine and concomitant desensitization of cα4β2-nAChR in smokers shifts the balance ih favor of signaling with strong direct and indirect stimulatory effects on cancer cells.Recently, it was suggested that social stress stimulates human transplanted lung cancer growth by increasing α7-nAChR-mediated stress neurotransmitter signaling.Moreover, acetylcholine (ACh), the physiological ligand of nAChR, works as an autocrine or paracrine growth factor in lung cancer.Different genome-wide association studies (GWAS) have associated single nucleotide polymorphisms (SNPs), in the nAChR encoding genes cluster CHRNA3/A5/B4, with both nicotine-dependence and lung cancer incidence and susceptibility.Recently, it was shown that different variants of human cα9-nAChR subunit protein differentially control both the regulation of bronchial cell proliferation and the susceptibility to the tumorigenic transformation by NNK.Different nAChR antagonists (i.e.curare) inhibit lung cancer growth, suggesting that nAChR may be valuable targets in lung cancer interventions.In conclusion, although the avoidance of tobacco smoking is the best cancer prevention, the continuous understanding of the roles of nAChR in the development and progression of lung cancer may offers novel opportunities for both the prevention and therapy of cancer.