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Fifty years of tobacco carcinogenesis research: from mechanisms to early detection and prevention of lung cancer.

Cancer Prev Res (Phila). 2014 Jan;7(1):1-8

Authors: Hecht SS, Szabo E

Abstract
The recognition of the link between cigarette smoking and lung cancer in the 1964 Surgeon General's Report initiated definitive and comprehensive research on the identification of carcinogens in tobacco products and the relevant mechanisms of carcinogenesis. The resultant comprehensive data clearly illustrate established pathways of cancer induction involving carcinogen exposure, metabolic activation, DNA adduct formation, and consequent mutation of critical genes along with the exacerbating influences of inflammation, cocarcinogenesis, and tumor promotion. This mechanistic understanding has provided a framework for the regulation of tobacco products and for the development of relevant tobacco carcinogen and toxicant biomarkers that can be applied in cancer prevention. Simultaneously, the recognition of the link between smoking and lung cancer paved the way for two additional critical approaches to cancer prevention that are discussed here: detection of lung cancer at an early, curable stage, and chemoprevention of lung cancer. Recent successes in more precisely identifying at-risk populations and in decreasing lung cancer mortality with helical computed tomography screening are notable, and progress in chemoprevention continues, although challenges with respect to bringing these approaches to the general population exist. Collectively, research performed since the 1964 Report demonstrates unequivocally that the majority of deaths from lung cancer are preventable. Cancer Prev Res; 7(1); 1-8. ©2014 AACR.

PMID: 24403288 [PubMed - in process]

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Detection of Lung Cancer by FDG-PET Cancer Screening Program: A Nationwide Japanese Survey.

Anticancer Res. 2014 Jan;34(1):183-9

Authors: Minamimoto R, Senda M, Jinnouchi S, Terauchi T, Yoshida T, Uno K, Iinuma T, Murano T, Nakashima R, Inoue T

Abstract
UNLABELLED: Aim: The aim of this study was to analyze the lung cancer detection rate in asymptomatic individuals by the Fluorine-18 fluorodeoxyglucose-positron emission tomography FDG-PET cancer screening program in Japan.
MATERIALS AND METHODS: A total of 153,775 asymptomatic individuals underwent the FDG-PET cancer screening program; the 854 cases with findings that indicated suspected lung cancer by any detection method were analyzed.
RESULTS: Among the 854 cases, 319 were verified as lung cancer. The relative sensitivity and positive predictive value (PPV) of FDG-PET were 86.5% and 38.9% for lung cancer, respectively. The sensitivity of PET/computed tomography (CT) scanner was higher than that of dedicated PET (100.0% vs. 63.2%), indicating that CT imaging was effective for lung cancer screening. The majority of lung carcinomas detected by FDG-PET screening were UICC stage IA or IB, but detection of smaller or less invasive carcinomas was limited.
CONCLUSION: The FDG-PET screening program in Japan detected lung cancer at an early stage.

PMID: 24403460 [PubMed - in process]

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From platinum compounds to targeted therapies in advanced thoracic malignancies.

Anticancer Res. 2014 Jan;34(1):477-82

Authors: Jakopovic M, Thomas A, Lopez-Chavez A

Abstract
Improved understanding of the molecular mechanisms involved in development, growth and spread of cancer have led to develpment of targeted therapies for many cancers. Based on their superior tolerability and efficacy, targeted therapies with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) or crizotinib are preferred first-line treatments over platinum-based chemotherapies in patients whose tumours harbour EGFR-activating mutations and anaplastic lymphoma kinase (ALK) translocations, respectively. Active areas of research in EGFR-mutant and ALK-translocated NSCLC include identification of mechanisms of resistance and overcoming them. Therapeutic targeting of several other targets including ROS, RET and discoidin domain receptor 2 (DDR2) tyrosine kinases are in early phases of clinical evaluation. Despite the advances in tumour genomic sequencing, a substantial fraction of patients with non-small cell lung cancer (NSCLC) do not have any targetable genetic alteration. Ongoing research is focused on identifying mechanisms of carcinogenesis in these patients. Targeted therapies in small cell lung cancer (SCLC) and thymic malignancies have not yielded meaningful clinical benefits, and platinum-based therapies remain the cornerstone of treating patients with advanced disease.

PMID: 24403504 [PubMed - in process]

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Platinum drugs and DNA repair mechanisms in lung cancer.

Anticancer Res. 2014 Jan;34(1):493-501

Authors: Bonanno L, Favaretto A, Rosell R

Abstract
The standard first-line treatment for around 80% of newly-diagnosed advanced non-small cell lung cancer (NSCLC) is chemotherapy. Currently, patients are allocated to chemotherapy on the basis of clinical conditions, comorbidities and histology. If feasible, platinum-based chemotherapy is considered as the most efficacious option. Due to the heterogeneity in terms of platinum-sensitivity among patients with NSCLC, great efforts have been made in order to identify molecular predictive markers of platinum resistance. Based on the mechanism of action of platinum, several components of DNA repair pathways have been investigated as potential predictive markers. The main DNA repair pathways involved in the repair of platinum-induced DNA damage are nucleotide excision repair and homologous recombination. The most studied potential predictive markers of platinum-sensitivity are Excision Repair Cross Complementing-1 (ERCC1) and Brest Cancer Type-I Susceptibility protein (BRCA1); however, increasing biological knowledge about DNA repair pathways suggests the potential clinical usefulness of integrated analysis of multiple DNA repair components.

PMID: 24403507 [PubMed - in process]