Molecular epidemiology of human cancer risk: gene-environment interactions and p53 mutation spectrum in human lung cancer: The p53 tumour suppressor gene is at the crossroads of a network of cellular pathways including cell cycle checkpoints, DNA repair, chromosomal segregation, and apoptosis. These pathways have evolved to maintain the stability of the genome during cellular stress. The high frequency of p53 mutations in human cancer is a reflection of the importance of p53 involvement in this network of pathways during human carcinogenesis. The focus of this review is on the role of p53 and cancer susceptibility genes in the molecular pathogenesis and epidemiology of human lung cancer -

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An update on the role of epidermal growth factor receptor inhibitors in non-small cell lung cancer: Within the past 2 years, epidermal growth factor receptor (EGFR) inhibitors have moved from experimental agents to approved drugs for the management of advanced non-small cell lung cancer (NSCLC). The identification of mutations in the ATP-binding domain of the EGFR that predict for dramatic responses introduces the possibility of truly individualized therapy in a subset of advanced NSCLC patients. The fact that these mutations may be more prevalent in certain patient populations, including patients of Asian ethnicity, female gender, and never-smoker status, raises intriguing questions regarding the pathogenesis of lung cancer. Numerous questions have arisen regarding how to best incorporate EGFR-targeted agents into patient management, as well as the role of the clinical laboratory in these decisions and the design of future trials - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16459173&itool=iconabstr&query_hl=6&itool=pubmed_docsum

Multiple Oncogenic Changes (K-RASV12, p53 Knockdown, Mutant EGFRs, p16 Bypass, Telomerase) Are Not Sufficient to Confer a Full Malignant Phenotype on Human Bronchial Epithelial Cells: The researchers of this study have evaluated the contribution of three genetic alterations (p53 knockdown, K-RASV12, and mutant EGFR) to lung tumorigenesis using human bronchial epithelial cells (HBEC) immortalized with telomerase and Cdk4-mediated p16 bypass. The study results indicate that (a) the HBEC model system is a powerful new approach to assess the contribution of individual and combinations of genetic alterations to lung cancer pathogenesis; (b) a combination of four genetic alterations, including human telomerase reverse transcriptase over expression, bypass of p16/RB and p53 pathways, and mutant K-RASV12 or mutant EGFR, is still not sufficient for HBECs to completely transform to cancer; and (c) EGFR tyrosine kinase inhibitors inhibit the growth of preneoplastic HBEC cells, suggesting their potential for chemoprevention - http://cancerres.aacrjournals.org/cgi/content/full/66/4/2116