Genomic and Proteomic Profiling of Lung Cancers: Lung Cancer Classification in the Age of Targeted Therapy

2005 ◽  
Vol 23 (14) ◽  
pp. 3219-3226 ◽  
Author(s):  
Matthew Meyerson ◽  
David Carbone
Keyword(s):  
Lung Cancer ◽  
Messenger Rna ◽  
Expression Profiles ◽  
Tumor Development ◽  
Cancer Classification ◽  
Proteomic Profiling ◽  
Lung Cancers ◽  
Development And Differentiation ◽  
Patient Prognosis ◽  
Cancer Multiple

Both proteomic and genomic methods offer promise for the classification of human lung carcinomas. This review summarizes the range of proteomic methods in development for lung cancer classification, and describes a number of recent analyses of messenger RNA expression in lung cancer. Multiple independent studies of mRNA expression profiles in lung adenocarcinoma have proven highly reproducible. Analyses of the relationship between expression profiles and tumor development and differentiation, the presence or absence of specific pathogenic mutations, patient prognosis and survival after surgical treatment, and specific histopathology all appear to be promising.

scholarly journals Clinical Significance of MicroRNA Expression Profiles and Polymorphisms in Lung Cancer Development and Management

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Francesca Megiorni ◽  
Antonio Pizzuti ◽  
Luigi Frati
Keyword(s):  
Lung Cancer ◽  
Expression Profiles ◽  
Genetic Alterations ◽  
Cancer Development ◽  
Industrialized Countries ◽  
Lung Cancers ◽  
Novel Treatments ◽  
Novel Mirna ◽  
Clinical Biomarkers ◽  
Development And Management

Lung cancers account for a huge percentage of death in industrialized countries, and hence there is an increasing call for the development of novel treatments. These malignancies are caused by a combination of environmental factors, principally cigarette smoking and genetic alterations. MicroRNAs (miRNAs) are a recently discovered class of regulatory noncoding small RNAs with a significance in numerous biological processes. Strong evidence links miRNA impaired expression profiles and pathways to the etiology of several diseases, including neoplasia. This paper focuses on the emerging role of miRNA function in lung cancer development with particular highlighting on the use of miRNA profiles and polymorphisms for the molecular and biological characterization of tumor pulmonary growth and progression. Furthermore, we underline the potential utility of lung cancer-associated miRNAs as clinical biomarkers with a diagnostic, prognostic, and therapeutic significance and give emphasis to the promising novel miRNA-based curative strategies.

The Impact of Gene Expression Microarrays in the Evaluation of Lung Carcinoma Subtypes and DNA Copy Number

2008 ◽  
Vol 132 (10) ◽  
pp. 1562-1565
Author(s):  
Montserrat Sanchez-Cespedes
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Gene Amplification ◽  
Genetic Background ◽  
Expression Profiles ◽  
Global Analysis ◽  
Tumor Development ◽  
Gene Expression Profiles ◽  
Molecular Alterations ◽  
The Impact

Abstract Context.—The development of targeted therapies creates a need to accurately classify tumors. Among the more pressing needs are the identification of the complete catalog of genes that are altered in cancer and the accurate discrimination of tumors based on their genetic background. Objectives.—To discuss the use of gene expression profiles to recapitulate the pathology and to distinguish the genetic background of non–small cell lung cancer. Also, to comment on using global analysis of gene expression to identify chromosomal regions carrying clusters of highly expressed genes, likely due to gene amplification. Gene amplification at these regions may target the activation of an oncogene critical to tumor development and potentially important in therapy. Data Sources.—Review of relevant, recent literature on molecular alterations and expression analysis in lung cancer. Conclusions.—The complexity of genetic and epigenetic alterations and the cell type of origin confer marked patterns of gene expression to lung tumors, which differentiate different tumor entities.

scholarly journals Prognostic value of S1PR1 and Correlations with Immune Infiltrates in Breast and Lung Cancers

2020 ◽  
Author(s):  
Yufeng Liu ◽  
Limei Zhong ◽  
Lijuan Li ◽  
Shaohua Song ◽  
Donglin Cao
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Immune Cell ◽  
Tumor Development ◽  
Disease Free Survival ◽  
Lung Squamous Cell Carcinoma ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Poor Overall Survival ◽  
Lung Cancers

Abstract Sphingosine-1-phosphate receptor (S1PR1) is involved in vascular development, a key process in tumorigenesis. Our study evaluated its roles in tumor development and prognosis. In particular, S1PR1 expression data were obtained from the TIMER and Oncomine database. We used a bioinformatics approach to evaluate its relationship with prognosis, co-expressed and regulatory genes, correlations with tumor immune cell infiltration and correlations with immune infiltration markers. S1PR1 was significantly lower expression in breast and lung cancer than in corresponding normal tissues. Lower S1PR1 expression was related to poor overall survival and disease-free survival in breast and lung cancer. A functional network analysis suggested that S1PR1 regulates vasculogenesis. In addition, S1PR1 levels were significantly related to infiltrating CD8+, CD4+ T cells, macrophages, and neutrophils in breast invasive carcinoma; CD8+ T cells, macrophages, neutrophils, and DCs in lung adenocarcinoma; and with B cells, CD8+, CD4+ T cells, macrophages, neutrophils and DCs in lung squamous cell carcinoma. Furthermore, S1PR1 levels were correlated with multiple immune marker sets in breast and lung cancer. The observed correlations between S1PR1 and both prognosis and immune cell infiltration provide a foundation for further research on its immunomodulatory role in cancer.

scholarly journals N6-methyladenosine induced miR-143-3p promotes the brain metastasis of lung cancer via regulation of VASH1

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Hongsheng Wang ◽  
Qianqian Deng ◽  
Ziyan Lv ◽  
Yuyi Ling ◽  
Xue Hou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Expression Profiles ◽  
Primary Lung Cancer ◽  
Lung Cancers ◽  
Lung Cancer Patients ◽  
Cancer Pathogenesis ◽  
Cancer Tissues

Abstract Background Brain metastasis (BM) is one of the principal causes of mortality for lung cancer patients. While the molecular events that govern BM of lung cancer remain frustrating cloudy. Methods The miRNA expression profiles are checked in the paired human BM and primary lung cancer tissues. The effect of miR-143-3p on BM of lung cancer cells and its related mechanisms are investigated. Results miR-143-3p is upregulated in the paired BM tissues as compared with that in primary cancer tissues. It can increase the invasion capability of in vitro blood brain barrier (BBB) model and angiogenesis of lung cancer by targeting the three binding sites of 3’UTR of vasohibin-1 (VASH1) to inhibit its expression. Mechanistically, VASH1 can increase the ubiquitylation of VEGFA to trigger the proteasome mediated degradation, further, it can endow the tubulin depolymerization through detyrosination to increase the cell motility. m6A methyltransferase Mettl3 can increase the splicing of precursor miR-143-3p to facilitate its biogenesis. Moreover, miR-143-3p/VASH1 axis acts as adverse prognosis factors for in vivo progression and overall survival (OS) rate of lung cancer. Conclusions Our work implicates a causal role of the miR-143-3p/VASH1 axis in BM of lung cancers and suggests their critical roles in lung cancer pathogenesis.

scholarly journals Current Molecular-Targeted Therapies in NSCLC and Their Mechanism of Resistance

Cancers ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 224 ◽  
Author(s):  
Zachary Schrank ◽  
Gagan Chhabra ◽  
Leo Lin ◽  
Tsatsral Iderzorig ◽  
Chike Osude ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Side Effects ◽  
Targeted Therapies ◽  
Lung Cancer Patient ◽  
Acquired Resistance ◽  
Cancer Biomarkers ◽  
Lung Cancers ◽  
Clinical Challenge ◽  
Current Therapies ◽  
Patient Prognosis

Lung cancer is treated with many conventional therapies, such as surgery, radiation, and chemotherapy. However, these therapies have multiple undesirable side effects. To bypass the side effects elicited by these conventional treatments, molecularly-targeted therapies are currently in use or under development. Current molecularly-targeted therapies effectively target specific biomarkers, which are commonly overexpressed in lung cancers and can cause increased tumorigenicity. Unfortunately, several molecularly-targeted therapies are associated with initial dramatic responses followed by acquired resistance due to spontaneous mutations or activation of signaling pathways. Acquired resistance to molecularly targeted therapies presents a major clinical challenge in the treatment of lung cancer. Therefore, to address this clinical challenge and to improve lung cancer patient prognosis, we need to understand the mechanism of acquired resistance to current therapies and develop additional novel therapies. This review concentrates on various lung cancer biomarkers, including EGFR, ALK, and BRAF, as well as their potential mechanisms of drug resistance.

scholarly journals Gene expression profiles of small-cell lung cancers: Molecular signatures of lung cancer

2006 ◽  
Author(s):  
Masaya Taniwaki ◽  
Yataro Daigo ◽  
Nobuhisa Ishikawa ◽  
Atsushi Takano ◽  
Tatsuhiko Tsunoda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Small Cell ◽  
Molecular Signatures ◽  
Small Cell Lung ◽  
Lung Cancers

Enhancing 18F-FDG-PET/CT analysis in lung cancer patients

2015 ◽  
Vol 54 (06) ◽  
pp. 247-254 ◽  
Author(s):  
A. Kapfhammer ◽  
T. Winkens ◽  
T. Lesser ◽  
A. Reissig ◽  
M. Steinert ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Image Fusion ◽  
Chest Wall ◽  
Fdg Pet ◽  
Ct Image ◽  
Lung Cancers ◽  
Pet Ct ◽  
Peripheral Lung ◽  
Fdg Pet Ct ◽  
Tumour Infiltration

SummaryAim: To retrospectively evaluate the feasibility and value of CT-CT image fusion to assess the shift of peripheral lung cancers with/-out chest wall infiltration, comparing computed tomography acquisitions in shallow-breathing (SB-CT) and deep-inspiration breath-hold (DIBH-CT) in patients undergoing FDG-PET/ CT for lung cancer staging. Methods: Image fusion of SB-CT and DIBH-CT was performed with a multimodal workstation used for nuclear medicine fusion imaging. The distance of intrathoracic landmarks and the positional shift of tumours were measured using semitransparent overlay of both CT series. Statistical analyses were adjusted for confounders of tumour infiltration. Cutoff levels were calculated for prediction of no-/infiltration. Results: Lateral pleural recessus and diaphragm showed the largest respiratory excursions. Infiltrating lung cancers showed more limited respiratory shifts than non-infiltrating tumours. A large respiratory tumour-motility accurately predicted non-infiltration. However, the tumour shifts were limited and variable, limiting the accuracy of prediction. Conclusion: This pilot fusion study proved feasible and allowed a simple analysis of the respiratory shifts of peripheral lung tumours using CT-CT image fusion in a PET/CT setting. The calculated cutoffs were useful in predicting the exclusion of chest wall infiltration but did not accurately predict tumour infiltration. This method can provide additional qualitative information in patients with lung cancers with contact to the chest wall but unclear CT evidence of infiltration undergoing PET/CT without the need of additional investigations. Considering the small sample size investigated, further studies are necessary to verify the obtained results.

Drug Combinatorial Therapies for the Treatment of KRAS Mutated Lung Cancers

2019 ◽  
Vol 19 (23) ◽  
pp. 2128-2142 ◽  
Author(s):  
Hao He ◽  
Chang Xu ◽  
Zhao Cheng ◽  
Xiaoying Qian ◽  
Lei Zheng
Keyword(s):  
Lung Cancer ◽  
Adjuvant Therapy ◽  
Combination Therapy ◽  
Clinical Benefit ◽  
Poor Prognosis ◽  
Egfr Mutations ◽  
Kras Mutations ◽  
Lung Cancers ◽  
Egfr Tki ◽  
Egfr Tkis

: KRAS is the most common oncogene to be mutated in lung cancer, and therapeutics directly targeting KRAS have proven to be challenging. The mutations of KRAS are associated with poor prognosis, and resistance to both adjuvant therapy and targeted EGFR TKI. EGFR TKIs provide significant clinical benefit for patients whose tumors bear EGFR mutations. However, tumors with KRAS mutations rarely respond to the EGFR TKI therapy. Thus, combination therapy is essential for the treatment of lung cancers with KRAS mutations. EGFR TKI combined with inhibitors of MAPKs, PI3K/mTOR, HDAC, Wee1, PARP, CDK and Hsp90, even miRNAs and immunotherapy, were reviewed. Although the effects of the combination vary, the combined therapeutics are one of the best options at present to treat KRAS mutant lung cancer.

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