title: Nicotine-induced resistance of non-small cell lung cancer to treatment--possible mechanisms.
abstract: Cigarette smoking is the leading risk factor of lung cancer. Data from several clinical studies suggest that continuation of smoking during therapy of tobacco-related cancers is associated with lower response rates to chemotherapy and/or radiotherapy, and even with decreased survival. Although nicotine--an addictive component of tobacco--is not a carcinogen, it may influence cancer development and progression or effectiveness of anti-cancer therapy. Several in vitro and in vivo trials have evaluated the influence of nicotine on lung cancer cells. The best known mechanisms by which nicotine impacts cancer biology involve suppression of apoptosis induced by certain drugs or radiation, promotion of proliferation, angiogenesis, invasion and migration of cancer cells. This effect is mainly mediated by membranous nicotinic acetylcholine receptors whose stimulation leads to sustained activation of such intracellular pathways as PI3K/Akt/mTOR, RAS/RAF/MEK/ERK and JAK/STAT, induction of NF-κB activity, enhanced transcription of mitogenic promoters, inhibition of the mitochondrial death pathway or stimulation of pro-angiogenic factors. We herein summarize the mechanisms underlying nicotine's influence on biology of lung cancer cells and the effectiveness of anti-cancer therapy.
authors.affiliation: Chemotherapy Department, Medical University of Łódź, Copernicus Memorial Hospital, Łódź
authors.forename: Rafał
authors.initials: R
authors.lastname: Czyżykowski
authors.affiliation: Chemotherapy Department, Medical University of Łódź, Copernicus Memorial Hospital, Łódź
authors.forename: Joanna
authors.initials: J
authors.lastname: Połowinczak-Przybyłek
authors.affiliation: Chemotherapy Department, Medical University of Łódź, Copernicus Memorial Hospital, Łódź
authors.forename: Piotr
authors.initials: P
authors.lastname: Potemski
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology / Q000532:radiotherapy; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology / Q000532:radiotherapy; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D009385:Neoplastic Processes; D009389:Neovascularization, Pathologic / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D012907:Smoking / Q000009:adverse effects*
chemical_list: D011978:Receptors, Nicotinic; D009538:Nicotine