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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lung cancer continues to be the leading cause of cancer death worldwide, and nonsmall cell lung cancer(NSCLC) is the most common type of lung cancer. Despite many clinical trials of platinum-based chemotherapy in combination with various drugs, the median survival time of NSCLC patients remains poor. The overall 5-year survival rate is approximately 15%, and has improved only marginally over the last few decades despite the introduction of new therapeutic agents. A recent milestone in this field has been the development of molecular-targeting drugs, among which gefitinib and erlotinib targeting the epidermal growth factor receptor (EGFR) have improved the efficacy of therapy for NSCLC. Anti-angiogenetic drug, such as bevacizumab, had become clinical use in the treatment for NSCLC. Moreover, discovery of EML4-ALK made the marvelous progress in cancer research in NSCLC. In this review, we discuss about the development of molecular-targeting drugs, such as EGFR-TKI, anti-angiogenetic drug, and EMLA-ALK inhibitors.
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PMID:[Molecular targeted therapy in lung cancer]. 2095 28

Primary adenocarcinoma with signet-ring cell component (Ad-SRCC) of the lung has been well characterized clinicopathologically and histologically, but their genetics has rarely been investigated. A recent report suggesting an association between Ad-SRCC and EML4-ALK fusion prompted us to undertake a histological, immunohistochemical, and molecular analysis of 10 cases of primary Ad-SRCC identified out of 699 lung adenocarcinomas (1.4%). Most of the Ad-SRCCs showed characteristic architectural as well as cytological features including cohesive clustering of signet-ring cells, a solid/acinar growth pattern, and alveolar filling at the tumor periphery. Diffuse co-expression of TTF-1 and p63 was observed in half of the Ad-SRCCs, and this immunoprofile has not been recognized previously. Four Ad-SRCCs (40%) harbored ALK translocations detected by reverse-transcriptase polymerase chain reaction, fluorescence in situ hybridization, and immunohistochemistry. One new EML4-ALK fusion variant was identified. One ALK-rearranged tumor showed focal squamous differentiation. None of the present Ad-SRCCs had EGFR or KRAS mutations, regardless of ALK status. This study successfully utilized tumor histology alone to identify a subset of adenocarcinomas showing a high rate of ALK translocation. The characteristic histology, immunoprofile, frequent ALK translocation, and total lack of EGFR or KRAS mutations, may suggest that Ad-SRCC forms a histologically/molecularly coherent subgroup of adenocarcinoma.
Lung Cancer 2011 Jun
PMID:Frequent ALK rearrangement and TTF-1/p63 co-expression in lung adenocarcinoma with signet-ring cell component. 2103 15

Despite considerable progress in the development of individualized targeted therapies of tumor diseases, identification of additional reliable target molecules is still mandatory. One of the most recent targets is microtubule-associated human EML4 generating a fusion-type oncogene with ALK demonstrating marked transforming activity in lung cancer. Since EML4 is a poorly characterized protein with regard to expression, function and regulation in human tissue, specimens of human tumor and tumor-free tissues obtained from patients with NSCLC were analyzed to determine the cellular localization. All tissue samples have been previously fixed with the novel HOPE-technique and paraffin embedded. Determination of both gene expression and protein levels of EML4 were performed using RT-PCR, in situ hybridization as well as immunohistochemistry, respectively. In human NSCLC tissue samples, possible regulation of EML4 transcription upon chemotherapy with combinations of most established cytotoxic drugs for NSCLC treatment was also studied employing the recently established ex vivo tissue culture model STST. In normal lung, both marked mRNA and protein levels of EML4 were localized in alveolar macrophages. In contrast, lung tumor tissues always showed consistent transcriptional expression in situ and by RT-PCR. Stimulation of NSCLC tissues with chemotherapeutics revealed heterogeneous effects on EML4 mRNA levels. Based on its expression patterns in both tumor-free lung and NSCLC tissues, human EML4 is likely to be closely associated with processes involved in local inflammation of the lung as well as with tumor behavior. Thus, our results suggest that EML4 may have the potential as a therapeutic target molecule in NSCLC chemotherapy.
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PMID:Expression analysis of EML4 in normal lung tissue and non-small cell lung cancer (NSCLC) in the absence and presence of chemotherapeutics. 2110 21

Lung cancer remains one of the leading causes of cancer-related death in developed countries. Although lung adenocarcinomas with EGFR mutations or EML4-ALK fusions respond to treatment by epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibition, respectively, squamous cell lung cancer currently lacks therapeutically exploitable genetic alterations. We conducted a systematic search in a set of 232 lung cancer specimens for genetic alterations that were therapeutically amenable and then performed high-resolution gene copy number analyses. We identified frequent and focal fibroblast growth factor receptor 1 (FGFR1) amplification in squamous cell lung cancer (n = 155), but not in other lung cancer subtypes, and, by fluorescence in situ hybridization, confirmed the presence of FGFR1 amplifications in an independent cohort of squamous cell lung cancer samples (22% of cases). Using cell-based screening with the FGFR inhibitor PD173074 in a large (n = 83) panel of lung cancer cell lines, we demonstrated that this compound inhibited growth and induced apoptosis specifically in those lung cancer cells carrying amplified FGFR1. We validated the FGFR1 dependence of FGFR1-amplified cell lines by FGFR1 knockdown and by ectopic expression of an FGFR1-resistant allele (FGFR1(V561M)), which rescued FGFR1-amplified cells from PD173074-mediated cytotoxicity. Finally, we showed that inhibition of FGFR1 with a small molecule led to significant tumor shrinkage in vivo. Thus, focal FGFR1 amplification is common in squamous cell lung cancer and associated with tumor growth and survival, suggesting that FGFR inhibitors may be a viable therapeutic option in this cohort of patients.
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PMID:Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. 2128 2

The fusion gene EML4-ALK (echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene) was recently identified as a novel genetic alteration in non-small cell lung cancer (NSCLC). EML4-ALK translocations correlate with specific clinical and pathological features, in particular lack of EGFR and K-ras mutations, and may be associated with resistance to EGFR tyrosine-kinase inhibitors (TKIs). Here, we report a case of a patient with a concomitant EGFR mutation and ALK translocation resistant to erlotinib. Considering this report, ALK status should be investigated in unexplained cases of EGFR-TKI-resistance of EGFR mutated NSCLCs.
Lung Cancer 2011 Feb
PMID:EGFR and EML4-ALK gene mutations in NSCLC: a case report of erlotinib-resistant patient with both concomitant mutations. 2116 33

Globally, lung cancer remains the most common cause of cancer-related death. In recent years, it has become clear that development of rational molecular targeted therapies is critical to improve the outcomes of patients with lung cancer. A better understanding of the tumor biology is crucial to achieve this goal. Several new findings in the field of tumor biology were presented at the 46th Annual Meeting of the American Society of Clinical Oncology. Novel genetic mutations were identified in pleural mesothelioma using array-based technologies. Several studies on the development and testing of new molecular diagnostic tests to detect epidermal growth factor receptor tyrosine kinase mutations and EML4-ALK (Echinoderm Microtubule-associated Protein like 4 Anaplastic Lymphoma Receptor Tyrosine Kinase) fusion gene were presented as well.
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PMID:Summary of presentations from the 46th Annual Meeting of the American Society of Clinical Oncology (2010) focus on tumor biology and biomarkers related to lung cancer. 2120 84

Lung cancer is a leading cause of cancer-related mortality across the world. Although the majority of lung cancer is attributed to tobacco smoke, approximately 25% of lung cancers worldwide occur in lifelong never smokers. Over the past decades, the bulk of research on this disease suggested that several genetic, environmental, hormonal, and viral factors might increase the risk of lung cancer among never smokers. However, there has been no dominant risk factor whose significance has been validated across racial and ethnic groups. However, this subset of lung cancers has received renewed attention due to the introduction of the epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitors showing the dramatic therapeutic response on selected patients with activating EGFR mutations which occur more commonly in never smokers. The treatment strategy blocking EGFR pathway in EGFR-mutant lung cancer represents a remarkable example of molecular targeted therapies which completely repress tumor by inhibition of driving oncogenes. More recently, a surprising positive effect of an ALK inhibitor on EML4-ALK-positive lung cancer has been suggested that lung cancer in never smokers is likely to be an assemblage of molecularly defined subsets which would be a good candidate for personalized diagnostic and therapeutic approaches.
Lung Cancer 2011 Apr
PMID:Lung cancer in never smokers: change of a mindset in the molecular era. 2127 54

The introduction of newer therapies and approaches for management has led to a renewed excitement in the field of lung cancer. This trend has continued in 2010 with the adoption of the new staging system recommended by the International Association for the Study of Lung Cancer (IASLC). Novel targets, such as EML4-ALK, have been identified and agents targeting these abnormalities have shown promise in uncontrolled clinical trials, while other strategies, including combining targeted agents with cytotoxic chemotherapy in unselected patients, have not proven to be successful. This review summarizes important recent clinical advances that could have a significant impact on the future care of patients with lung cancer.
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PMID:Lung cancer management in 2010. 2136 Dec 48

While lung cancer is the leading cause of cancer deaths worldwide, the molecular mechanism underlying its carcinogenesis is mainly unknown. We have discovered a small, fusion-type tyrosine kinase EML4-ALK that is generated through a tiny inversion within the short arm of human chromosome 2. Transgenic mice expressing EML4-ALK in lung developed hundreds of lung cancer nodules soon after birth, but such nodules were readily eradicated upon treatment with an ALK inhibitor. Clinical trials for EML4-ALK-positive lung cancer with an ALK inhibitor is ongoing, with its interim results being highly promising.
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PMID:[ALK inhibitor]. 2136 58

Smoking status is essential to know when taking care of a lung cancer patient. Never-smoking patients account for 15% of lung cancer patients, more often women and adenocarcinoma. Environmental tobacco smoke and occupational exposure could be important risk factors. Lung cancer in never-smoker appears to be a distinct entity from lung cancer in smoker, with specific molecular characteristics such as frequent EGFR mutations. New molecular targets are on investigation, such as EML4-ALK translocation. Treatment of lung cancer in never-smoker is getting different from that of smoker with more efficacy of molecular targeted therapies.
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PMID:[Lung cancer in never smoker: Epidemiology, molecular profiles and treatment]. 2142 Feb 71


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