Nicotinic acetylcholine receptor as a pharmacological target in lung cancer

Kononenko V, Bele T, Novak S, Kri┼żaj I, Drobne D, Turk T.
[ site ] Acta Biologica, 2023

Tobacco smoking is a major risk factor for the development of lung cancer, as tobacco smoke contains many carcinogens. Nicotine, which is not classified as a carcinogen, is the main component of tobacco, responsible for addiction and recent research suggests that nicotine, independent of other tobacco components, may contribute to the development and progression of cancer. Nicotine, as an agonist of nicotinic acetylcholine receptors (nAChRs), promotes cell proliferation, prevents apoptosis, and has an important role in promoting angiogenesis and metastasis of cancer cells. The realisation that nAChRs are involved in the development and progression of lung cancer has raised the idea of using nAChR antagonists that would counteract the adverse effect of nicotine. Currently, there are only a few nAChR antagonists for which anticancer efficacy has been investigated. Many of the known antagonists do not act selectively on nAChR subtypes that are overexpressed in lung cancer cells. Nonselective nAChR antagonists can cause adverse side effects by acting on nAChR subtypes expressed on non-cancerous cells. In order to avoid such side effects, it is necessary to ensure that a given antagonist acts predominantly on cancer cells. This can be achieved by using nanodelivery systems that are preferentially uptaken by cancer cells. In this article, we present the latest achievements in the development of drugs for the treatment of lung cancer based on nAChR antagonists delivered to the site of action by nanoparticles.