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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An increasing number of chromosomal aberrations is being identified in solid tumors providing novel biomarkers for various types of cancer and new insights into the mechanisms of carcinogenesis. We applied next generation sequencing technique to analyze the transcriptome of the non-small cell lung carcinoma (NSCLC) cell line H2228 and discovered a fusion transcript composed of multiple exons of ALK (anaplastic lymphoma receptor tyrosine kinase) and PTPN3 (protein tyrosine phosphatase, nonreceptor Type 3). Detailed analysis of the genomic structure revealed that a portion of genomic region encompassing Exons 10 and 11 of ALK has been translocated into the intronic region between Exons 2 and 3 of PTPN3. The key net result appears to be the null mutation of one allele of PTPN3, a gene with tumor suppressor activity. Consistently, ectopic expression of PTPN3 in NSCLC cell lines led to inhibition of colony formation. Our study confirms the utility of next generation sequencing as a tool for the discovery of somatic mutations and has led to the identification of a novel mutation in NSCLC that may be of diagnostic, prognostic, and therapeutic importance.
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PMID:Discovery of ALK-PTPN3 gene fusion from human non-small cell lung carcinoma cell line using next generation RNA sequencing. 2233 42

In this article, we will summarize some of the aspects covered by key opinion leaders at the Perspectives in Lung Cancer Congress, particularly focusing on the most recent molecular discoveries in non-small-cell lung cancer which, we believe, will have a deep impact on the clinical development of novel targeted therapies in the future. We discuss genetic alterations in squamous cell carcinoma, crizotinib therapy for ALK-positive tumors, the latest information on antiangiogenic therapies, and strategies aimed at interfering with the Ras-Raf-MEK pathway in more detail. A special emphasis is placed on the potential implications that each covered point will have for the management of advanced non-small-cell lung cancer.
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PMID:Novel molecular trends in the management of advanced non-small-cell lung cancer. 2271 89

In recent years, better understanding of the molecular biology of non-small-cell lung carcinoma (nsclc) has led to a revolution in the work-up of these neoplasms. As a pathology diagnosis, "nsclc" without further attempt at subclassification is no longer accepted as a standard of care; separating squamous cell carcinoma from adenocarcinoma and large-cell carcinoma carries implications for prognosis and treatment decisions. Currently, detection of the presence in nsclc of mutations involving the epidermal growth factor receptor (EGFR) gene and fusion of the N-terminal portion of the protein encoded by EML4 (echinoderm microtubule-associated protein-like 4 gene) with the intracellular signaling portion of the receptor tyrosine kinase encoded by ALK (anaplastic lymphoma kinase gene)-that is, EML4-ALK-and variants has become routine in many centres because patients having tumours harbouring such alterations might benefit from tyrosine kinase inhibitors as part of their treatment regimen.The purpose of the present review is to highlight important aspects of the screening for molecular derangements in nsclc and to briefly discuss the emergence of possible future biomarkers.
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PMID:The role of molecular pathology in non-small-cell lung carcinoma-now and in the future. 2278 8

Targeting of the epidermal growth factor receptor (egfr) pathway has become routine practice in the treatment of lung carcinoma. As more health authorities approve targeted compounds in a variety of treatment lines, use of this approach is expected only to increase.Gefitinib, an oral tyrosine kinase inhibitor (tki), is approved by Health Canada in the first-line setting of advanced non-small-cell lung carcinoma (nsclc) for tumours that harbour the EGFR gene mutation. Erlotinib, another tki, is currently approved in advanced nsclc in the second- and third-line settings.The side-effect profile of this class of drugs is unique. Hematologic toxicity is seldom seen. The most frequent side effects are rash and diarrhea. Although no randomized trials have addressed treatment of the side effects of this class of drugs, some basic principles of management have been agreed on and can likely improve patient compliance and decrease inappropriate dose reduction. The prognostic and predictive implications of side effects are also evolving.Finally, the ALK fusion mutation is being recognized as a mutation driver. The use of crizotinib (again, a tki) in this setting awaits approval. The side-effect profile of crizotinib is interesting and is also reviewed here.
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PMID:Supportive care treatments for toxicities of anti-egfr and other targeted agents. 2278 12

The traditional distinction between small cell lung cancer and non-small cell lung cancer (NSCLC) is no longer sufficient for treatment planning. It is advised to handle small diagnostic specimens prudently because they are often the only specimen available for molecular analysis. Pathologists are experiencing pressure to subclassify lung carcinoma based on extremely small tumor samples, because NSCLC tumor subtyping is now essential to determine molecular testing strategies. Evaluation for EGFR mutations and ALK rearrangements are now considered to be the standard of care in advanced-stage pulmonary adenocarcinomas. Immunohistochemical stains can aid in subclassifying NSCLC, but performing these ancillary studies can significantly reduce the quantity of tissue available for molecular tests, requiring careful balancing of these 2 needs. The pathologist plays a pivotal role in facilitating clear and timely communication between the clinical oncology care team and the molecular laboratory to ensure that the appropriate tests are ordered and optimal material is submitted for testing.
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PMID:Molecular pathology of non-small cell lung cancer: a practical guide. 2291 49

Lung cancer remains the leading cause of cancer-related mortality in the world despite advances in the field of cancer therapeutics. Traditional treatment with empirically chosen cytotoxic chemotherapeutic agents, have given small, but real survival benefits. Recent advances and insights into molecular pathogenesis of lung cancers have provided some novel molecular targets, offering newer strategies and agents that are tumor specific. Studies have identified mutations in specific genes that are involved in driving the development of lung cancer and so it is important to subsequently target them with specific drugs thus changing paradigms of management of this type of cancer. Recently, Lung Cancer Mutation Consortium (LCMC) has identified at least one of the many recognized "driver mutations" in nearly two thirds of the patients with advanced cancer. This study suggests that identification of driver mutations can help in molecular targeted therapeutics and in addition supplant tumor histology in guiding treatment decisions, identifying subset of patients who may benefit therapy. This review focuses on these mutations identified in specific genes serving as "drivers" of lung tumorigenesis and suggests that clear promise for the future of lung cancer treatment is indeed personalized therapy with drugs chosen according to the patient mutation profile. Most clinically relevant translational advances made in genes involved in lung tumorigenesis namely EML4-ALK fusions, HER2, PIK3CA, AKT, BRAF, MAP2K1, MET mutations and amplifications along with the well established EGFR and KRAS mutations are discussed in the context of NSCLCs. These studies emphasize the need for treatment management based on mutation profile along with routine histology based classification of these tumors in future for a directed therapy and thus a better therapeutic outcome.
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PMID:Targetable "driver" mutations in non small cell lung cancer. 2294 8

We report the results of whole-genome and transcriptome sequencing of tumor and adjacent normal tissue samples from 17 patients with non-small cell lung carcinoma (NSCLC). We identified 3,726 point mutations and more than 90 indels in the coding sequence, with an average mutation frequency more than 10-fold higher in smokers than in never-smokers. Novel alterations in genes involved in chromatin modification and DNA repair pathways were identified, along with DACH1, CFTR, RELN, ABCB5, and HGF. Deep digital sequencing revealed diverse clonality patterns in both never-smokers and smokers. All validated EFGR and KRAS mutations were present in the founder clones, suggesting possible roles in cancer initiation. Analysis revealed 14 fusions, including ROS1 and ALK, as well as novel metabolic enzymes. Cell-cycle and JAK-STAT pathways are significantly altered in lung cancer, along with perturbations in 54 genes that are potentially targetable with currently available drugs.
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PMID:Genomic landscape of non-small cell lung cancer in smokers and never-smokers. 2298 Sep 76

Few descriptions of miliary brain metastases have been reported. We report the case of an adenocarcinoma of the lung associated with metachronous miliary brain and lung metastases with an echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) gene translocation. The patient was treated with crizotinib and showed a twelve-month progression-free survival. Clinicians should be attentive of the evolution of brain metastases with patients presenting EML4-ALK translocation.
Lung Cancer 2012 Dec
PMID:Adenocarcinoma of the lung with miliary brain and pulmonary metastases with echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase translocation treated with crizotinib: a case report. 2299 80

The high incidence and poor prognosis of lung cancer represent a major health problem. Currently, about 20% of lung cancer patients can benefit from targeted therapy after identification of EGFR, ALK or HER2 somatic mutations or rearrangements. Other mutations, such as KRas oncogenic mutation, are still orphans of validated targeted therapy. In this review, we describe the different mouse models of lung carcinoma. We then illustrate the interests of such models for the identification and validation of new therapeutic targets, for the study of secondary resistance and for their use as preclinical models and for new therapeutic strategy tests.
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PMID:[The mouse as preclinical models of lung cancer]. 2313 2

Most of the cases of non-small-cell lung cancer (NSCLC) are diagnosed at an advanced stage and are treated with platinum-doublet chemotherapy. However, some patients are refractory to this treatment. The aim of this study was to identify the clinical and molecular characteristics of patients with refractory disease. All consecutive patients between 2003 and 2006, who received a platinum-doublet chemotherapy as first-line treatment for stage IIIb-IV NSCLC, were included. Refractory patients were defined as early progressive disease (PD) at the first evaluation of chemotherapy according to WHO criteria. The clinical, histo-pathological, and molecular characteristics (EGFR: exon 19, 20, 21 and KRAS: exon 2 by PCR sequencing; ALK by immunohistochemistry) and survival of refractory patients with initial PD (r-patients) and controlled disease (c-patients) were compared by univariate analyses. Factors that differed between the two groups (p-value <0.25 in univariate analyses) were entered into multivariate analysis. In this study, 178 patients were included. The first tumor assessment was carried out after a median of three cycles (range 1-4). Forty-six (25.8%) patients were refractory. Clinical presentation was similar between r- and c-patients. The sarcomatoid histological subtype was more common in r-patients than c-patients (10.9% vs. 1.5%, respectively; p=0.057). The proportion of EGFR (5.2% vs. 9.6%, p=0.224) and KRAS mutations (11.1% vs. 5.7%, p=0.357), and the expression of ALK (6.3% vs. 2.5%, p=0.327) did not differ significantly between the two groups. In multivariate analysis, sarcomatoid histological subtype was the only factor associated with early PD (OR=7.50; 95%CI: 1.02-55.45; p=0.048). r-Patients had significantly shorter survival than c-patients (median 5 months (IQR 3.2-9.9) vs. 15.4 months (IQR 9.9-22.5), respectively; p<0.0001). In conclusion, patients with early PD under platinum-doublet chemotherapy had shorter survival than c-patients. Sarcomatoid histological subtype was the only independent factor associated with early PD.
Lung Cancer 2013 Feb
PMID:Clinical and molecular features in patients with advanced non-small-cell lung carcinoma refractory to first-line platinum-based chemotherapy. 2315 58


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