Abstract
Non-small cell lung cancer (NSCLC) in non-, and especially in never-smoking patients is considered a biologically unique type of lung cancer, since risk factors and tumorigenic conditions, other than tobacco smoke, come into play. In this review article, we comprehensively searched and summarized the current literature with the aim to outline what exactly triggers lung cancer in non-smokers. Changes in the tumor microenvironment, distinct driver genes and genetic pathway alterations that are specific for non-smoking patients, as well as lifestyle-related risk factors apart from tobacco smoke are critically discussed. The data we have reviewed highlights once again the importance of personalized cancer therapy, i.e., careful molecular and genetic assessment of the tumor to provide tailored treatment options with optimum chances of good response—especially for the subgroups of never-smokers.
Highlights
Lung cancer is the second most common incident cancer diagnosis in men, and the fourth most common cancer diagnosis in women, accounting for most cancer-related deaths in both men and women, with 1.7 million global deaths a year [1,2,3]
Cancers 2019, 11, 204 is the occurrence of certain molecular subtypes, enabling the specific treatment with Previous epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) or other agents [19,20]. Such genetic alterations and patterns of mutation that are specific for lung cancer have primarily been outlined for AC, whereas no genetic mutations have been linked to squamous cell carcinoma (SCC) especially not for non-smokers [4]
The immune cells are part of the harmful tumor microenvironment and can even contribute to tumor growth, invasion and metastatic spread [49]. This is proven by certain biologicals that have recently been established as targeted treatment options for lung cancer, targeting for instance cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), or programmed death 1 (PD-1)-receptor and PD-1 ligand (PD-L1) which are targeted by nivolumab and atezolizumab [49]
Summary
Lung cancer is the second most common incident cancer diagnosis in men, and the fourth most common cancer diagnosis in women, accounting for most cancer-related deaths in both men and women, with 1.7 million global deaths a year [1,2,3]. Genome-wide studies clearly indicated that the underlying tumor biology in lung cancers of non-smokers (meaning never-smokers and patients with a negligible history of smoking and small likelihood that the tumor was smoking-related) differs dramatically from smoking-related lung cancer, featuring a different pattern of molecular alterations [10,13,14,15,16,17]. Cancers 2019, 11, 204 is the occurrence of certain molecular subtypes (oncogene-addicted lung cancer), enabling the specific treatment with Previous epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) or other agents [19,20] Such genetic alterations and patterns of mutation that are specific for lung cancer have primarily been outlined for AC, whereas no genetic mutations have been linked to squamous cell carcinoma (SCC) especially not for non-smokers [4]. We will highlight and discuss the knowledge of distinct molecular and epidemiological differences between lung cancer in never-smokers with a special emphasis and separation between different lung cancer histology
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