Lung Cancer

Herbst, Roy S.; Heymach, John V.; Lippman, Scott M.

doi:10.1056/nejmra0802714

Cited by 2,288 publications

(2,022 citation statements)

References 122 publications

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“…[221][222][223] The discovery of other molecular resistance aberrations, such as MET kinase amplification or mutations of EML4-ALK fusion, which cause constitutive activation of RAS/RAF1/MAP2K1, has provided further insight and validation into factors limiting the therapeutic efficacy of EGFR inhibitors. 53,148,224 The mystery as to why all tumors harboring drug-sensitive EGFR mutations do not respond to treatment with EGFR TKI inhibitors is yet to be resolved. Clinical investigations have shown that the presence of other genetic alterations affecting signaling pathways downstream of EGFR may have a crucial role.…”

Section: Other Genomic Alterationsmentioning

confidence: 99%

Molecular pathology of lung cancer: key to personalized medicine

et al. 2012

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The majority of lung adenocarcinoma patients with epidermal growth factor receptor-(EGFR) mutated or EML4-ALK rearrangement-positive tumors are sensitive to tyrosine kinase inhibitors. Both primary and acquired resistance in a significant number of those patients to these therapies remains a major clinical problem. The specific molecular mechanisms associated with tyrosine kinase inhibitor resistance are not fully understood. Clinicopathological observations suggest that molecular alterations involving so-called 'driver mutations' could be used as markers that aid in the selection of patients most likely to benefit from targeted therapies. In this review, we summarize recent developments involving the specific molecular mechanisms and markers that have been associated with primary and acquired resistance to EGFR-targeted therapy in lung adenocarcinomas. Understanding these mechanisms may provide new treatment avenues and improve current treatment algorithms.

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Section: Other Genomic Alterationsmentioning

confidence: 99%

Molecular pathology of lung cancer: key to personalized medicine

et al. 2012

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“…The 5‐year survival rates for lung cancer in 2005–2009 ranged from 15% to 20% in most countries (Cheng et al., 2016; Wang et al., 2013). Non‐small cell lung cancer (NSCLC) is the most common histological type, comprising approximately 80%–85% of cases (Herbst, Heymach, & Lippman, 2008; Reck, Heigener, Mok, Soria, & Rabe, 2013). While the distribution of histologies varies among countries, the two most common NSCLC histological subtypes are squamous cell carcinoma and the non‐squamous cell carcinomas, of which adenocarcinoma is the most common.…”

Section: Introductionmentioning

confidence: 99%

Systemic therapy treatment patterns in patients with advanced non-small cell lung cancer (NSCLC): PIvOTAL study

et al. 2017

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The aim of this multinational retrospective cohort study, conducted at academic and community oncology centres, was to describe real‐world treatment patterns for patients with a confirmed diagnosis of advanced/metastatic (stage IIIB/IV) non‐small cell lung cancer (NSCLC) who initiated first‐line systemic therapy from January 2011 through June 2014. The study included 1265 patients in Italy, Spain, Germany, Australia, Korea, Taiwan and Brazil. The proportion of patients with squamous versus non‐squamous NSCLC was approximately 20% versus 75%, and associated patient demographic characteristics were similar in all countries, excepting race. Patients with squamous NSCLC were predominantly male and current/ex‐smokers. Biomarker tests were performed for the majority of patients with non‐squamous NSCLC, ranging from 54% (Brazil) to 91% in Taiwan, where, of those tested, 68% with non‐squamous NSCLC had positive epidermal growth factor receptor (EGFR)‐mutation status; in other countries the EGFR‐positive percentages ranged from 17% (Spain/Brazil) to 40% (Korea). Platinum‐based regimens were the most common first‐line therapy in all countries except Taiwan, where gefitinib was the most common first‐line agent. Median overall survival ranged from 9.3 months (Brazil) to 25.5 months (Taiwan). The diagnostic and treatment patterns recorded in this study were heterogeneous but largely in line with NSCLC guidelines during the study period.

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“…The high mortality of NSCLC is largely attributable to late diagnosis, when metastases are present. 2 The molecular mechanisms governing metastasis of NSCLC remain poorly understood.Metastasis is a complex, multistep process, involving migration and invasion of malignant cells from the primary tumor to blood vessels, intravasation, and survival in the circulation, and ultimately extravasation, colonization, and formation of secondary tumor at distant target organs. 3 Each of these events is classically driven by the acquisition of genetic and/or epigenetic traits in tumor cells and the cooperation of nonneoplastic stromal cells.…”

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confidence: 99%

“…1 Non-small-cell lung cancer (NSCLC) accounts for~80-85% of lung cancers. 2 Only 20-30% of NSCLC are radically resectable and the majority of lung cancer patients succumb to the disease. The high mortality of NSCLC is largely attributable to late diagnosis, when metastases are present.…”

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LAMC2 enhances the metastatic potential of lung adenocarcinoma

et al. 2015

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Lung cancer is the number one cancer killer, and metastasis is the main cause of high mortality in lung cancer patients. However, mechanisms underlying the development of lung cancer metastasis remain unknown. Using genome-wide transcriptional analysis in an experimental metastasis model, we identified laminin γ2 (LAMC2), an epithelial basement membrane protein, to be significantly upregulated in lung adenocarcinoma metastatic cells. Elevated LAMC2 increased traction force, migration, and invasion of lung adenocarcinoma cells accompanied by the induction of epithelial-mesenchymal transition (EMT). LAMC2 knockdown decreased traction force, migration, and invasion accompanied by EMT reduction in vitro, and attenuated metastasis in mice. LAMC2 promoted migration and invasion via EMT that was integrin β1-and ZEB1-dependent. High LAMC2 was significantly correlated with the mesenchymal marker vimentin expression in lung adenocarcinomas, and with higher risk of recurrence or death in patients with lung adenocarcinoma. We suggest that LAMC2 promotes metastasis in lung adenocarcinoma via EMT and may be a potential therapeutic target. Cell Death and Differentiation (2015) 22, 1341-1352; doi:10.1038/cdd.2014.228; published online 16 January 2015Lung cancer is the leading cause of cancer-related death. 1 Non-small-cell lung cancer (NSCLC) accounts for~80-85% of lung cancers. 2 Only 20-30% of NSCLC are radically resectable and the majority of lung cancer patients succumb to the disease. The high mortality of NSCLC is largely attributable to late diagnosis, when metastases are present. 2 The molecular mechanisms governing metastasis of NSCLC remain poorly understood.Metastasis is a complex, multistep process, involving migration and invasion of malignant cells from the primary tumor to blood vessels, intravasation, and survival in the circulation, and ultimately extravasation, colonization, and formation of secondary tumor at distant target organs. 3 Each of these events is classically driven by the acquisition of genetic and/or epigenetic traits in tumor cells and the cooperation of nonneoplastic stromal cells. Increased or decreased expression of several genes in tumors has been found to be correlated with metastasis. 3 However, specific gene alterations that drive NSCLC metastasis remain largely elusive.Laminin γ2 (LAMC2) is a subunit of the heterotrimeric glycoprotein laminin-332 (LAM-332, formerly laminin-5), consisting of the α3, β3, and γ2 chains. Although LAMC2 is an important structural component of the epithelial basement membrane (BM) in various normal tissues, 4 there is an emerging evidence for a pathological role of LAMC2 monomer in cancer. It has been demonstrated that LAMC2 protein expression correlates with clinical outcome of stage I lung adenocarcinoma (ADC) patients. 5,6 In addition, noncontinuous expression pattern of LAMC2 predicts the prognosis of esophageal squamous cell carcinoma (SCC), 7 and secreted LAMC2 in the serum is associated with the aggressiveness of pancreatic cancer. 8 Besides, LAMC2 monom...

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Lung Cancer

Abstract: T h e ne w e ngl a nd jou r na l o f m e dic i ne n engl j med 359;13 www.nejm.org september 25, 2008

Cited by 2,288 publications

References 122 publications

Molecular pathology of lung cancer: key to personalized medicine

Molecular pathology of lung cancer: key to personalized medicine

Systemic therapy treatment patterns in patients with advanced non-small cell lung cancer (NSCLC): PIvOTAL study

LAMC2 enhances the metastatic potential of lung adenocarcinoma

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