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

TL;DR

This review explores how nicotinic acetylcholine receptors influence cancer growth and suggests targeting them for better cancer therapies.

Contribution

The paper highlights context-specific roles of nAChRs in cancer and proposes targeting shared signaling pathways for therapeutic benefit.

Findings

Certain nAChR subtypes activate tumorigenic pathways like EGFR/ERK1/2 and PI3K/AKT in cancer.

Src kinase and MAPK pathways are common in lung, breast, and prostate cancers despite different nAChR subunits.

Context-specific targeting of nAChRs could modulate shared signaling pathways for cancer treatment.

Abstract

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.

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