Lung cancers express an autocrine cholinergic loop in which secreted acetylcholine can stimulate tumor
growth through both nicotinic and muscarinic receptors. Because activation of mAChR and nAChR stimulates
growth; tumor growth can be stimulated by both locally synthesized acetylcholine as well as acetylcholine from
distal sources and from nicotine in the high percentage of lung cancer patients who are smokers. The stimulation of
lung cancer growth by cholinergic agonists offers many potential new targets for lung cancer therapy. Cholinergic
signaling can be targeted at the level of choline transport; acetylcholine synthesis, secretion and degradation; and
nicotinic and muscarinic receptors. In addition, the newly describe family of ly-6 allosteric modulators of nicotinic
signaling such as lynx1 and lynx2 offers yet another new approach to novel lung cancer therapeutics. Each of these
targets has their potential advantages and disadvantages for the development of new lung cancer therapies which
are discussed in this review.
Keywords: Cancer, acetylcholine, nicotine, nicotinic receptors, muscarinic receptors, lynx-1.
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