Special Issue "Lung Cancer"
Quicklinks
A special issue of Cancers (ISSN 2072-6694).
Deadline for manuscript submissions: closed (30 December 2010)
Special Issue Editor
Guest Editor
Prof. Dr. Gerolama Condorelli
Department of Cellular and Molecular Biology and Pathology, Istituto di Endocrinologia e Oncologia Sperimentale ‘‘G. Salvatore’’-Consiglio Nazionale delle Ricerche, Faculty of Biotechnological Science, ‘‘Federico II’’ University of Naples, I-80121 Naples, Italy
Website: https://www.docenti.unina.it/cercaDocente.do?cognome=condorelli&submit1=avvia+ricerca
E-Mail: gecondor@unina.it
Interests: apoptosis; cell death; TRAIL; microRNA; cell motility; chemotherapy resistance
Special Issue Information
Dear Colleagues,
Lung cancer is the leading cause of cancer death in both men and women worldwide. It is becoming apparent, through candidate gene and genome-wide approaches, that clinically evident lung cancers accumulate numerous clonal genetic and epigenetic alterations during a multistep process. These alterations include tumor suppressor gene inactivation and activation of growth or survival promoting oncogenes.
Despite advances in early detection and standard treatment, lung cancer is often diagnosed at an advanced stage and have poor prognoses. The development of innovative, targeted therapies may represent an alternative for the treatment of these cancers.
One of the most important factors that affect survival rate is resistance to therapeutic drugs. Thus development of effective therapeutic approaches is necessary for the management of these common cancers. MiRNAs are attractive drug targets since they regulate expression of many cellular proteins and are differentially
MicroRNAs are small noncoding RNAs that show expression loss or gain in most cancers, and there is growing evidence that they play substantial roles in the pathogenesis and prognosis of human malignancies.
The central focus of the special issue on “Lung Cancer” is identification of molecular pathways involved in lung tumorigenesis and therapeutic resistance. The main topics will include, but are not limited to, the role of cell death (e.g., apoptosis and necrosis) and cell survival pathways (e.g., autophagy) in tumorigenesis and chemotherapy resistance; role microRNAs and their targets in lung prognosis, diagnosis and response to therapy.
Thank you for your collaboration.
Prof. Dr. Gerolama Condorelli
Guest Editor
Submission
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed Open Access quarterly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 500 CHF (Swiss Francs).
English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.
Keywords
- lung cancer
- MicroRNAs
- apoptosis
- autophagy
- caspases
- cell death
- cell survival
- death receptors
- oncogenes
- tumor suppressor genes
Published Papers (11 papers)
|
Received: 15 September 2010; in revised form: 15 October 2010 / Accepted: 24 October 2010 / Published: 28 October 2010
Show/Hide Abstract
| Download PDF Full-text (238 KB)
Abstract: Recent lung cancer studies have focused on identifying the effects of single nucleotide polymorphisms (SNPs) in candidate genes, among which DNA repair genes are increasingly being studied. Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. In this study, we tried to assess reported studies of association between polymorphism of human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys and lung cancer. We conducted MEDLINE, Current Contents and Web of Science searches using "hOGG1", "lung cancer" and "polymorphism" as keywords to search for papers published (from January 1995 through August 2010). Data were combined using both a fixed effects (the inverse variance-weighted method) and a random effects (DerSimonian and Laird method) model. The Cochran Q test was used for the assessment of heterogeneity. Publication bias was assessed by both Begg’s and Egger’s tests. We identified 20 case-control studies in 21 different ethnic populations. As two studies were not in the Hardy-Weinberg equilibrium, 18 case-control studies in 19 different ethnic populations (7,792 cases and 9,358 controls) were included in our meta-analysis. Summary frequencies of the Cys allele among aucasians and Asians based on the random effects model were 20.9% (95% confidence interval (CI) = 18.9–22.9) and 46.1% (95% CI = 40.2–52.0), respectively. The distribution of the Cys allele was significantly different between Asians and Caucasians (P < 0.001). The Cys/Cys genotype was significantly associated with lung cancer risk in Asian populations (odds ratio = 1.27, 95% CI = 1.09–1.48) but not in Caucasian populations. This ethnic difference in lung cancer risk may be due to environmental factors such as cigarette smoking and dietary factors. Although the summary risk for developing lung cancer may not be large, lung cancer is such a common malignancy that even a small increase in risk can translate to a large number of excess lung cancer cases. As lung cancer is a multifactorial disease, further investigations of the gene-gene and gene-environment interactions on the hOGG1 polymorphism-associated lung cancer risk may help to better understand of the molecular pathogenesis of human lung cancer.
 |
|
Received: 20 October 2010; in revised form: 25 November 2010 / Accepted: 21 December 2010 / Published: 22 December 2010
Show/Hide Abstract
| Download PDF Full-text (1363 KB) | 
Abstract: EGFR and c-Met are both overexpressed in lung cancer and initiate similar downstream signaling, which may be redundant. To determine how frequently ligands that initiate signaling of both pathways are found in lung cancer, we analyzed serum for hepatocyte growth factor (HGF), transforming growth factor-alpha, and amphiregulin (AREG) in lung cancer cases and tobacco-exposed controls. HGF and AREG were both significantly elevated in cases compared to controls, suggesting that both HGF/c-Met and AREG/EGFR pathways are frequently active. When both HGF and AREG are present in vitro, downstream signaling to MAPK and Akt in non-small cell lung cancer (NSCLC) cells can only be completely inhibited by targeting both pathways. To test if dual blockade of the pathways could better suppress lung tumorigenesis in an animal model than single blockade, mice transgenic for airway expression of human HGF were treated with inhibitors of both pathways alone and in combination after exposure to a tobacco carcinogen. Mean tumor number in the group using both the HGF neutralizing antibody L2G7 and the EGFR inhibitor gefitinib was significantly lower than with single agents. A higher tumor K-ras mutation rate was observed with L2G7 alone compared to controls, suggesting that agents targeting HGF may be less effective against mutated K-ras lung tumors. This was not observed with combination treatment. A small molecule c-Met inhibitor decreased formation of both K-ras wild-type and mutant tumors and showed additive anti-tumor effects when combined with gefitinib. Dual targeting of c-Met/EGFR may have clinical benefit for lung cancer.
 |
|
Received: 30 December 2010; in revised form: 9 February 2011 / Accepted: 15 February 2011 / Published: 23 February 2011
Show/Hide Abstract
| Download PDF Full-text (420 KB) | Download XML Full-text
Abstract: Mastic oil from Pistacia lentiscus variation chia, a natural combination of bioactive terpenes, has been shown to exert anti-tumor growth effects against a broad spectrum of cancers including mouse Lewis lung adenocarcinomas (LLC). However, no studies have addressed its anti-metastatic actions. In this study, we showed that treatment of LLC cells with mastic oil within a range of non-toxic concentrations (0.01–0.04% v/v): (a) abrogated their Matrigel invasion and migration capabilities in transwell assays; (b) reduced the levels of secreted MMP-2; (c) restricted phorbol ester-induced actin remodeling and (d) limited the length of neo-vessel networks in tumor microenvironment in the model of chick embryo chorioallantoic membrane. Moreover, exposure of LLC and endothelial cells to mastic oil impaired their adhesive interactions in a co-culture assay and reduced the expression of key adhesion molecules by endothelial cells upon their stimulation with tumor necrosis factor-alpha. Overall, this study provides novel evidence supporting a multipotent role for mastic oil in prevention of crucial processes related to cancer metastasis.
 |
|
Received: 31 December 2010; in revised form: 20 February 2011 / Accepted: 1 March 2011 / Published: 3 March 2011
Show/Hide Abstract
| Download PDF Full-text (373 KB) | Download XML Full-text
Abstract: Lung cancer remains one of the most common cancer-related causes of death. This type of cancer typically develops over a period of many years, and if detected at an early enough stage can be eliminated by a variety of treatments including photodynamic therapy (PDT). A critical discussion on the clinical applications of PDT in lung cancer is well outside the scope of the present report, which, in turn focuses on mechanistic and other aspects of the photodynamic action at a molecular and cellular level. The knowledge of these issues at pre-clinical levels is necessary to develop, check and adopt appropriate clinical protocols in the future. This report, besides providing general information, includes a brief overview of present experimental PDT and provides some non-exhaustive information on current strategies aimed at further improving the efficacy, especially in regard to lung cancer cells.
|
|
Received: 7 January 2011; in revised form: 28 February 2011 / Accepted: 1 March 2011 / Published: 10 March 2011
Show/Hide Abstract
| Download PDF Full-text (871 KB) | Download XML Full-text
Abstract: The ErbB/EGFR/HER family of kinases consists of four homologous receptor tyrosine kinases which are important regulatory elements in many cellular processes, including cell proliferation, differentiation, and migration. Somatic mutations in, or over-expression of, the ErbB family is found in many cancers and is correlated with a poor prognosis; particularly, clinically identified mutations found in non-small-cell lung cancer (NSCLC) of ErbB1 have been shown to increase its basal kinase activity and patients carrying these mutations respond remarkably to the small tyrosine kinase inhibitor gefitinib. Here, we analyze the potential effects of the currently catalogued clinically identified mutations in the ErbB family kinase domains on the molecular mechanisms of kinase activation. Recently, we identified conserved networks of hydrophilic and hydrophobic interactions characteristic to the active and inactive conformation, respectively. Here, we show that the clinically identified mutants influence the kinase activity in distinctive fashion by affecting the characteristic interaction networks.
 |
|
Received: 29 December 2010; in revised form: 9 March 2011 / Accepted: 10 March 2011 / Published: 17 March 2011
Show/Hide Abstract
| Download PDF Full-text (308 KB) | Download XML Full-text
Abstract: Non-small cell lung cancer (NSCLC) is the most common cause of cancer related death in the world. Cisplatin and carboplatin are the most commonly used cytotoxic chemotherapeutic agents to treat the disease. These agents, usually combined with drugs such as gemcitabine or pemetrexed, induce objective tumor responses in only 20–30% of patients. Aberrant epigenetic regulation of gene expression is a frequent event in NSCLC. In this article we review the emerging evidence that epigenetics and the cellular machinery involved with this type of regulation may be key elements in the development of cisplatin resistance in NSCLC.
|
|
Received: 4 January 2011; in revised form: 18 March 2011 / Accepted: 31 March 2011 / Published: 1 April 2011
Show/Hide Abstract
| Download PDF Full-text (188 KB) | Download XML Full-text
Abstract: Lung cancer is still a leading cause of cancer mortality in the world. The incidence of lung cancer in developed countries started to decrease mainly due to global anti-smoking campaigns. However, the incidence of lung cancer in women has been increasing in recent decades for various reasons. Furthermore, since the screening of lung cancer is not as yet very effective, clinically applicable molecular markers for early diagnosis are much required. Lung cancer in women appears to have differences compared with that in men, in terms of histologic types and susceptibility to environmental risk factors. This suggests that female lung cancer can be derived by carcinogenic mechanisms different from those involved in male lung cancer. Among female lung cancer patients, many are non-smokers, which could be studied to identify alternative carcinogenic mechanisms independent from smoking-related ones. In this paper, we reviewed molecular susceptibility markers and genetic changes in lung cancer tissues observed in female lung cancer patients, which have been validated by various studies and will be helpful to understand the tumorigenesis of lung cancer.
|
|
Received: 7 March 2011; in revised form: 28 April 2011 / Accepted: 3 May 2011 / Published: 11 May 2011
Show/Hide Abstract
| Download PDF Full-text (286 KB) | Download XML Full-text
Abstract: Increasing evidence suggests that tomato lycopene may be preventive against the formation and the development of lung cancer. Experimental studies demonstrated that lycopene may inhibit the growth of several cultured lung cancer cells and prevent lung tumorigenesis in animal models through various mechanisms, including a modulation of redox status, cell cycle arrest and/or apoptosis induction, a regulation of growth factor signaling, changes in cell growth-related enzymes, an enhancement of gap junction communication and a prevention of smoke-induced inflammation. In addition, lycopene also inhibited cell invasion, angiogenesis, and metastasis. Several lycopene metabolites have been identified, raising the question as to whether the preventive effects of lycopene on cancer risk is, at least in part, due to its metabolites. Despite these promising reports, it is difficult at the moment to directly relate available experimental data to human pathophysiology. More well controlled clinical intervention trials are needed to further clarify the exact role of lycopene in the prevention of lung cancer cell growth. Such studies should take into consideration subject selection, specific markers of analysis, the levels of carotenoids being tested, metabolism and isomerization of lycopene, interaction with other bioactive food components. This article reviews data on the cancer preventive activities of lycopene, possible mechanisms involved, and the relationship between lycopene consumption and human cancer risk.
|
|
Received: 28 April 2011; in revised form: 1 June 2011 / Accepted: 7 June 2011 / Published: 10 June 2011
Show/Hide Abstract
| Download PDF Full-text (198 KB) | Download XML Full-text
Abstract: Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) cases comprise approximately 85% of the lung cancer cases. Before the era of target therapy, platinum-based doublet chemotherapy only led to a median survival of 8–9 months and a one-year survival of 30%–40% in patients with advanced NSCLC. In July 2002, gefitinib, a small-molecule epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), was approved for the treatment of patients with advanced NSCLC in Japan. After the widespread use of gefitinib in the treatment of NSCLC, there have been many new studies regarding the association between the clinical anticancer efficacy of gefitinib and the somatic EGFR mutation status in patients with NSCLC. This article summarizes the role of EGFR mutations in lung cancer and the use of EGFR antagonists in the treatment of lung cancer and its associated adverse effects.
|
|
Received: 3 June 2011; in revised form: 11 July 2011 / Accepted: 12 July 2011 / Published: 19 July 2011
Show/Hide Abstract
| Download PDF Full-text (250 KB) | Download XML Full-text
Abstract: Lung cancer is the leading cause of cancer deaths, with an overall survival of 15% at five years. Biomarkers that can sensitively and specifically detect lung cancer at early stage are crucial for improving this poor survival rate. Sputum has been the target for the discovery of non-invasive biomarkers for lung cancer because it contains airway epithelial cells, and molecular alterations identified in sputum are most likely to reflect tumor-associated changes or field cancerization caused by smoking in the lung. Sputum-based molecular biomarkers include morphology, allelic imbalance, promoter hypermethylation, gene mutations and, recently, differential miRNA expression. To improve the sensitivity and reproducibility of sputum-based biomarkers, we recommend standardization of processing protocols, bronchial epithelial cell enrichment, and identification of field cancerization biomarkers.
|
|
Received: 13 October 2011; in revised form: 29 November 2011 / Accepted: 6 December 2011 / Published: 14 December 2011
Show/Hide Abstract
| Download PDF Full-text (101 KB) | Download XML Full-text
Abstract: The development of lung cancer in humans can be divided into three steps: initiation, promotion and progression. This process is driven by alterations in related signal transduction pathways. These pathways signal the aberrant activation of NF-kappaB, a transcription factor that regulates the expression of genes important for lung tumorigenesis. Our current knowledge about the role of the NF-kappaB signaling pathway in the development of lung cancer has been bolstered by animal models demonstrating the connection between K-ras and tobacco induced lung transformation with NF-kappaB. Activation of downstream genes leads to cell proliferation, inhibition of apoptosis, angiogenesis, inflammation, invasion, and metastasis.
|
Last update: 25 September 2012
