alpha7-Nicotinic receptor antagonists at the beginning of a clinical era for NSCLC and Mesothelioma?
Of the human solid cancers, Non-Small Cell Lung Cancer (NSCLC) and Malignant Pleural Mesothelioma (MPM) display a natural history supporting the concept that they develop from multiple preneoplastic pathways. Recently, new evidence suggested that nicotinic Acetylcholine Receptors (nAChRs) play a significant role in lung cancer predisposition and natural history. This review is based on some translational research aimed at evaluating the potential therapeutic effect of nAChR antagonists on NSCLC and MPM. The background and rationale of this approach are based on the experimental observations that: (a) NSCLC and MPM cells express nAChRs and (b) the activation of these receptors by agonists, namely nicotine, inhibits apoptosis, whereas receptor antagonists have a pro-apoptotic effect.
Paleari
Laura
L
Lung Cancer Unit, National Cancer Research Institute, Genoa, Italy. laura.paleari@istge.it
Cesario
Alfredo
A
Fini
Massimo
M
Russo
Patrizia
P
D000494:Allosteric Regulation; D002118:Calcium / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008654:Mesothelioma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D008956:Models, Chemical; D009389:Neovascularization, Pathologic / Q000139:chemically induced; D018919:Neovascularization, Physiologic / Q000187:drug effects; D018722:Nicotinic Agonists / Q000494:pharmacology / Q000627:therapeutic use; D018733:Nicotinic Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D010997:Pleural Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012910:Snake Venoms / Q000494:pharmacology
D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D012910:Snake Venoms; D002118:Calcium