Nicotinic Acetylcholine Receptor Pathways in Cancer: From Psychiatric Clues to Therapeutic Opportunities

The prevalence of cancer poses significant challenges to treatment, largely because of drug resistance along with other side effects. Current studies have been investigating the growth factors more than other biologic tumor features, such as neurobiologic features. Here in this review, we highlight the role of nicotinic acetylcholine receptors (nAChRs) in cancer development with their context-dependent activation and downstream effectors.

Some nAChR subtypes stimulate tumorigenic pathways, EGFR/ERK1/2, PI3K/AKT, and MAPK, with varying responses based on the receptor subtype and tissue type. Notably, the Src kinase and MAPK pathways are common downstream effectors in lung, breast, and prostate cancers despite the variations in the predominant nAChR subunits in each cancer: α7 in lung, α9 in breast, and likely α5 and α7 in prostate tumors.

These findings underscore the importance of targeting nAChRs in a context-specific manner to modulate shared signaling pathways, particularly the acetylcholine-stimulated Src/MAPK pathway. This review also calls for more investigation on other neurotransmitters and potential common pathways, as implicated by psychological reports, to advance the understanding of cancer biology and therapies.