Early stage and locally advanced (non-metastatic) non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Crinò, Lucio; Weder, Walter; Meerbeeck, Jan P. van; Felip, Enriqueta

doi:10.1093/annonc/mdq207

Cited by 443 publications

(307 citation statements)

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“…Although adjuvant chemotherapy has been shown to increase survival by about 4% in stages II and III, its use is controversial in stage IB and associated with detrimental effect in stage IA. 42 Strong prognostic factors in early stages of lung cancer are desperately needed, which could discriminate patients with a higher risk of tumor recurrence who might benefit from adjuvant chemotherapy. A plethora of putative prognostic markers have been identified, but most have not been independently validated.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

LAMC2 enhances the metastatic potential of lung adenocarcinoma

et al. 2015

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“…Along with the development of theoretical and practical chemotherapy for tumors, we have already known the combination of two drugs such as platinum and non-platinum is the standard first-line therapy for NSCLC patients (Crino et al, 2010). During the targeted therapy era, targeted drugs, such as gefitinib and erlotinib, can effectively reduce the incidence of brain metastases in patients with NSCLC (Zeng et al, 2012) Several studies showed that RRM1, XRCC1, TUBB3 and TS expression in tumor cells are involved in platinum and non-platinum (Rabik et al, 2007;Takezawa et al, 2011;Xie et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Multiplex Real-time PCR for RRM1, XRCC1, TUBB3 and TS mRNA for Prediction of Response of Non-small Cell Lung Cancer to Chemoradiotherapy

Liu²,

Xue³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: This study was aimed to establish a novel method to simultaneously detect expression of four genes, ribonucleotide reductase subunit M1(RRM1), X-ray repair cross-complementing gene 1 (XRCC1), thymidylate synthase (TS) and class III β-tubulin (TUBB3), and to assess their application in the clinic for prediction of response of non-small cell lung cancer (NSCLC) to chemoradiotherapy. Materials and Methods: We have designed four gene molecular beacon (MB) probes for multiplex quantitative real-time polymerase chain reactions to examine RRM1, XRCC1, TUBB3 and TS mRNA expression in paraffin-embedded specimens from 50 patients with advanced or metastatic carcinomas. Twenty one NSCLC patients receiving cisplatinbased first-line treatment were analyzed. Results: These molecular beacon probes could specially bind to their target genes in homogeneous solutions. Patients with low RRM1 and XRCC1 mRNA levels were found to have apparently higher response rates to chemoradiotherapy compared with those with high levels of RRM1 and XRCC1 expression (p<0.05). The TS gene expression level was not significantly associated with chemotherapy response (p>0.05). Conclusions: A method of simultaneously detecting four molecular markers was successfully established and applied for evaluation of chemoradiotherapy response. It may be a useful tool in personalized cancer therapy.

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“…The management of NSCLC involves multidisciplinary approach and optimal use of the available treatment modalities. Guidelines recommend surgery or radical doses of radiotherapy along with chemotherapy for stage 1-3A, radical radiotherapy with chemotherapy for stage 3B and palliative chemotherapy with or without palliative radiotherapy or TKIs for stage 4 disease (Crino et al, 2010;Peters et al, 2012a;2012b). In actual practice, not all patients receive the optimum treatment (Vinod et al, 2010).…”

Section: Discussionmentioning

confidence: 99%