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Lung cancer biomarkers: State of the art.

Lung cancer is one of the deadliest cancers worldwide, with the highest incidence and mortality amongst all cancers. While the prognosis of lung cancer is generally grim, with 5-year survival rates of only 15%, there is hope, and evidence, that early detection of lung cancer can reduce mortality.

Today, only computed tomography screening has shown to lead to early detection and reduction in mortality, but is limited by being anatomic in nature, unable to differentiate between inflammatory and neoplastic pathways, and therefore, susceptible to false positives. There is increasing interest in biomarkers for lung cancer, especially those that predict metastatic risk. Some biomarkers like DNA mutations and epigenetic changes potentially require tissue from the at-risk site; some like serum proteins and miRNAs are minimally invasive, but may not be specific to the lung. In comparison, emerging biomarkers from exhaled breath, like volatile organic compounds (VOC), and exhaled breath condensate, e.g., small molecules and nucleic acids, have the potential to combine the best of both.

This mini review is intended to provide an overview of the field, briefly discussing the potential of what is known and highlighting the exciting recent developments, particularly with miRNAs and VOCs.

Cell of origin of lung cancer.

Lung cancer is the leading cause of cancer deaths worldwide, and current therapies are disappointing. Elucidation of the cell(s) of origin of lung cancer may lead to new therapeutics. In addition, the discovery of putative cancer-initiating cells with stem cell properties in solid tumors has emerged as an important area of cancer research that may explain the resistance of these tumors to currently available therapeutics.

Progress in our understanding of normal tissue stem cells, tumor cell of origin, and cancer stem cells has been hampered by the heterogeneity of the disease, the lack of good in vivo transplantation models to assess stem cell behavior, and an overall incomplete understanding of the epithelial stem cell hierarchy. As such, a systematic computerized literature search of the MEDLINE database was used to identify articles discussing current knowledge about normal lung and lung cancer stem cells or progenitor cells.

In this review, we discuss what is currently known about the role of cancer-initiating cells and normal stem cells in the development of lung tumors.

PMID: 23599688 [PubMed - as supplied by publisher]

Targeted agents in non-small cell lung cancer therapy: What is there on the horizon?

Lung cancer is a heterogeneous group of diseases. There has been much research in lung cancer over the past decade which has advanced our ability to treat these patients with a more personalized approach.

The scope of this paper is to review the literature and give a broad understanding of the current molecular targets for which we currently have therapies as well as other targets for which we may soon have therapies. Additionally, we will cover some of the issues of resistance with these targeted therapies. The molecular targets we intend to discuss are epidermal growth factor receptor (EGFR), Vascular endothelial growth factor (VEGF), anaplastic large-cell lymphoma kinase (ALK), KRAS, C-MET/RON, PIK3CA. ROS-1, RET Fibroblast growth factor receptor (FGFR). Ephrins and their receptors, BRAF, and immunotherapies/vaccines.

This manuscript only summarizes the work which has been done to date and in no way is meant to be comprehensive.

Current evidence on the relationship between five polymorphisms in the matrix metalloproteinases (MMP) gene and lung cancer risk: a meta-analysis.

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Current evidence on the relationship between five polymorphisms in the matrix metalloproteinases (MMP) gene and lung cancer risk: a meta-analysis.

Gene. 2013 Mar 15;517(1):65-71

Authors: Hu C, Wang J, Xu Y, Li X, Chen H, Bunjhoo H, Xiong W, Xu Y, Zhao J

Abstract
PURPOSE: Matrix metalloproteinase (MMP) 1, MMP2, MMP3 and MMP9 are important members of the MMP family. Recently, many studies have been carried out on the association between polymorphisms of MMP1-1607 1G/2G, MMP2-735 C/T, MMP2-1306 C/T, MMP3-1171 5A/6A and MMP9-1562 C/T and lung cancer risk. However the results of these studies remained inconclusive due to conflicting results from different case-control studies. To clarify these associations, we conducted a meta-analysis.
METHODS: We conducted a comprehensive search in Medline, EMBASE, OVID and Chinese Biomedical Literature Database (date from Jan 2000 to Aug 2012). Overall and subgroup analysis by the ethnicity of study population was carried out. Odds ratio (OR) with 95% confidence interval (95%CI) was used to assess the strength of the association.
RESULTS: There were 17 studies involving five polymorphic sites in four MMP genes. For MMP1-1607,increased lung cancer risk was found under dominant model (MMP1-1607 1G/2G: OR=1.14, 95%CI=1.03-1.26, P=0.01), but not in the Caucasian population. For MMP2-1306 C/T, T polymorphism decreased lung cancer risk under dominant and recessive models (dominant, OR=0.63, 95%CI=0.46-0.88, P=0.0006; recessive, OR=0.61, 95%CI=0.38-0.99, P=0.04). For MMP9-1562 C/T, TT genotype decreased this risk under the recessive model (OR=0.38, 95%CI=0.19-0.75, P=0.005), but not in the Asian population. For MMP2-735 C/T and MMP3-1171 5A/6A, there was no association between this polymorphism and lung cancer risk under the dominant and recessive models.
CONCLUSIONS: MMP1-1607 1G/2G polymorphism increased lung cancer risk in Asians. It was also found that MMP2-1306 C/T polymorphism decreased lung cancer risk in Asians, while MMP9-1562 C/T polymorphism decreased lung cancer risk in Caucasians. No significant difference was found in any genotype of MMP2-735 C/T and MMP3-1171 5A/6A. Further studies with larger sample sizes should be carried out.

PMID: 23313298 [PubMed - indexed for MEDLINE]

Diagnostic yield of combined bronchoscopy and endobronchial ultrasonography, under LungPoint guidance for small peripheral pulmonary lesions.

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Diagnostic yield of combined bronchoscopy and endobronchial ultrasonography, under LungPoint guidance for small peripheral pulmonary lesions.

Respirology. 2013 Apr 16;

Authors: Tamiya M, Okamoto N, Sasada S, Shiroyama T, Morishita N, Suzuki H, Yoshida E, Hirashima T, Kawahara K, Kawase I

Abstract
BACKGROUND AND OBJECTIVE: The yield of biopsy performed during bronchoscopy is reduced if the lesion is smaller than 30 mm. We evaluated the performance of a new diagnostic technique combining endobronchial ultrasonography with a guide sheath (EBUS-GS) and a virtual bronchoscopic navigation system, LungPoint, for the diagnosis of small (≤30 mm) peripheral pulmonary lesions (PPLs). METHODS: Between May 2011 and December 2011we recruited 68 consecutive patients presenting with a PPLs 30 mm or less in diameter determined by chest computed tomography. We used the LungPoint system before bronchoscopy to identify the bronchus into which the bronchoscope should be advanced. We used a thin bronchoscope,. EBUS-GS was performed using an endoscope ultrasonography system equipped with a 20-MHz mechanical radial-type probe. We used a guide sheath with an external diameter of 1.95 mm, thin forceps, and brushing. RESULTS: The diagnostic yield of the 68 PPLs was 77.9%; it was 83.7% and 68.0% for the malignant and benign lesions respectively. Notably, 3 cases were diagnosed by transbronchial needle-aspiration cytology alone. Univariate and multivariate analyses showed that the EBUS probe localisation was the most significant contributor to successful diagnosis (diagnostic yield: within vs. adjacent to the lesion = 92.1% vs. 60.0%, respectively; p = 0.004 and p = 0.003, respectively). CONCLUSIONS: The combination of EBUS-GS and LungPoint was useful for diagnosing small PPLs.

PMID: 23586738 [PubMed - as supplied by publisher]

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