Nicotinic acetylcholine receptors in cancer: Limitations and prospects

Abstract

Nicotinic acetylcholine receptors (nAChRs) have long been considered to solely mediate neurotransmission. However, their widespread distribution in the human body suggests a more diverse physiological role. Additionally, the expression of nAChRs is increased in certain cancers, such as lung cancer, and has been associated with cell proliferation, epithelial-to-mesenchymal cell transition, angiogenesis and apoptosis prevention. Several compounds that interact with these receptors have been identified as potential therapeutic agents. They have been tested as drugs for treating nicotine addiction, alcoholism, depression, pain and Alzheimer's disease. This review focuses on nAChR-mediated signalling in cancer, presenting opportunities for the development of innovative nAChR-based anticancer drugs. It displays the differences in expression of each nAChR subunit between normal and cancer cells for selected cancer types, highlighting their possible involvement in specific cases. Antagonists of nAChRs that could complement existing cancer therapies are summarised and critically discussed. We hope that this review will stimulate further research on the role of nAChRs in cancer potentially leading to innovative cancer therapies.

Keywords: Angiogenesis; Antagonist; Apoptosis; Cancer; Mitochondria; Signalling; Therapy; nAChR.