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Neuronal Acetylcholine Nicotinic Receptors as New Targets for Lung Cancer Treatment

[ Vol. 22 , Issue. 14 ]

Author(s):

Vanessa Mucchietto, Arianna Crespi, Francesca Fasoli, Francesco Clementi and Cecilia Gotti   Pages 2160 - 2169 ( 10 )

Abstract:


Lung cancer is the leading cause of cancer-related deaths worldwide. Smoking accounts for approximately 70% of the cases of non– small cell lung cancer (NSCLC) and 90% of the cases of small-cell lung cancer (SCLC), although some patients develop lung cancer without a history of smoking. </p> <p> Nicotine is the most active addictive component of tobacco smoke. It does not initiate tumorigenesis in humans and rodents, but it alters the pathophysiology of lung cells by inducing the secretion of growth factors, neurotransmitters and cytokines, and promotes tumour growth and metastases by inducing cell cycle progression, migration, invasion, angiogenesis and the evasion of apoptosis. Most of these effects are a result of nicotine binding and activation of cell-surface neuronal nicotinic acetylcholine receptors (nAChRs) and downstream intracellular signalling cascades, and many are blocked by nAChR subtype-selective antagonists. </p> <p> Recent genome-wide association studies have revealed single nucleotide polymorphisms of nAChR subunits that influence nicotine dependence and lung cancer. </p> <p> This review describes the molecular basis of nAChR structural and functional diversity in normal and cancer lung cells, and the genetic alterations facilitating smoking-induced lung cancers. It also summarises current knowledge concerning the intracellular pathways activated by nicotine and other compounds present in tobacco smoke.

Keywords:

Neuronal nicotinic acetylcholine receptors, lung cancer, acetylcholine, nicotine, NNK, antagonists, polymorphisms.

Affiliation:

, , , , CNR, Via Vanvitelli 32, 20129 Milan, Italy.



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