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

Lung adenocarcinomas have diverse genetic and morphological backgrounds and are usually classified according to their distinct oncogenic mutations (or so-called driver mutations) and histological subtypes (the de novo classification proposed by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society [IASLC/ATS/ERS]). Although both these classifications are essential for personalized treatment, their integrated clinical effect remains unclear. Therefore, we analyzed 981 lung adenocarcinomas to detect the potential correlation and combined effect of oncogenic mutations and histological subtype on prognosis. Analysis for oncogenic mutations included the direct sequencing of EGFR, KRAS, HER2, BRAF, PIK3CA, ALK, and RET for oncogenic mutations/rearrangements, and a rereview of the IASLC/ATS/ERS classification was undertaken. Eligible tumors included 13 atypical adenomatous hyperplasia/adenocarcinoma in situ, 20 minimally invasive adenocarcinomas, 901 invasive adenocarcinomas, 44 invasive mucinous adenocarcinomas, and three other variants. The invasive mucinous adenocarcinomas had a lower prevalence of EGFR mutations but a higher prevalence of KRAS, ALK, and HER2 mutations than invasive adenocarcinomas. Smoking, a solid predominant pattern, and a mucinous component were independently associated with fewer EGFR mutations. The ALK rearrangements were more frequently observed in tumors with a minor mucinous component, while the KRAS mutations were more prevalent in smokers. In addition, 503 patients with stage I-IIIA tumors were analyzed for overall survival (OS) and relapse-free survival. The stage and histological pattern were independent predictors of relapse-free survival, and the pathological stage was the only independent predictor for the OS. Although patients with the EGFR mutations had better OS than those without the mutations, no oncogenic mutation was an independent predictor of survival. Oncogenic mutations were associated with the novel IASLC/ATS/ERS classification, which facilitates a morphology-based mutational analysis strategy. The combination of these two classifications might not increase the prognostic ability, but it provides essential information for personalized treatment.
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PMID:Oncogenic mutations are associated with histological subtypes but do not have an independent prognostic value in lung adenocarcinoma. 2515 23

Oncogenic drivers in lung non-small-cell lung cancer (NSCLC) are considered mutually exclusive, but a review of the literature reveals that concomitant EGFR mutations and ALK rearrangement may occur in a subset of NSCLC. We report here a case of pulmonary adenocarcinoma with concomitant EGFR mutation in exon 21 (L858R) and ALK rearrangement in naive and relapsed tumors. Tumor cells seem to harbor both gene alterations and the patient had a long-lasting response both to EGFR inhibitor in second line and ALK inhibitor once tumor progressed. A speculative discussion on molecular mechanisms underlying this uncommon phenomenon and practical points about epidemiologic, clinicopathologic features and therapeutic options in this intriguing subset of double-positive tumor are reported.
Lung Cancer 2014 Nov
PMID:Concomitant EGFR mutation and ALK rearrangement in lung adenocarcinoma is more frequent than expected: report of a case and review of the literature with demonstration of genes alteration into the same tumor cells. 2531 89

Molecular selection has led to the successful use of novel tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancers (NSCLCs). For instance, mutations in EGFR and translocations and fusions in ALK render tumor cells sensitive to some TKIs, leading to substantial clinical benefits. Molecular testing such as DNA sequencing or fragment analysis following PCR, and evaluation of copy number and gene positioning by FISH, have been developed and used clinically to identify mutations/fusions. Meanwhile, TKIs to target actionable mutations/fusions in several other oncogenes are being evaluated. High-throughput sequencing can provide therapy-predictive information as well as identify novel targetable genomic alterations. In this article, we report our experience enabling single-gene testing, and our evolution to panel-based next-generation sequencing.
Lung Cancer Manag 2014 Aug 01
PMID:From single-gene to multiplex analysis in lung cancer, challenges and accomplishments: a review of a single institution's experience. 2558 Jan 59

We herein present a rare case of an EML4-ALK positive patient. A 61-year-old man was diagnosed with locoregional non-small cell lung cancer (NSCLC). No EGFR mutations were detected, and therefore the ALK rearrangement was evaluated using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and the reverse transcription PCR (RT-PCR) method for EML4-ALK. All methods showed a positive result and, therefore, the patient was treated with crizotinib with a good therapeutic response. However, a detailed RT-PCR analysis and sequencing revealed an unexpected 138 bp insertion of attractin-like 1 (ATRNL1) gene into the EML4-ALK fusion gene. In our case, the positive therapeutic response suggests that ATRNL1 insertion does not affect EML4-ALK's sensitivity to crizotinib. This case shows great EML4-ALK heterogeneity and also that basic detection methods (IHC, FISH) cannot fully specify ALK rearrangement but in many cases a full specification seems to be important for an effective TKI indication, and sequencing ALK variants might contribute to optimized patient selection.
Lung Cancer 2015 Mar
PMID:Identification of atypical ATRNL1 insertion to EML4-ALK fusion gene in NSCLC. 2560 88

The aim of the Clinical and Molecular Staging of Stage I-IIp Lung Cancer Project is to identify molecular variables that improve the prognostic and predictive accuracy of TMN classification in stage I/IIp non-small cell lung cancer (NSCLC). Clinical data and lung tissue, tumor and blood samples will be collected from 3 patient cohorts created for this purpose. The prognostic protein signature will be validated from these samples, and micro-RNA, ALK, Ros1, Pdl-1, and TKT, TKTL1 y G6PD expression will be analyzed. Tissue inflammatory markers and stromal cell markers will also be analyzed. Methylation of p16, DAPK, RASSF1a, APC and CDH13 genes in the tissue samples will be determined, and inflammatory markers in peripheral blood will also be analyzed. Variables that improve the prognostic and predictive accuracy of TNM in NSCLC by molecular staging may be identified from this extensive analytical panel.
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PMID:Biological Marker Analysis as Part of the CIBERES-RTIC Cancer-SEPAR Strategic Project on Lung Cancer. 2561 75

We describe a case of dysgeusia that developed gradually over one week after initiation of crizotinib administration for treatment of ALK-positive non-small cell lung cancer, necessitating discontinuation of the agent. The symptom was accompanied by progressive loss in appetite and body weight. Alectinib, a novel alternative ALK inhibitor, was administered and has been successfully continued without any toxicity, including dysgeusia. The present case indicates that dysgeusia is an important toxicity associated with crizotinib, which could adversely affect nutritional condition and quality of life. We describe the clinical course and present a review of crizotinib-induced dysgeusia.
Lung Cancer 2015 Apr
PMID:Successful treatment of crizotinib-induced dysgeusia by switching to alectinib in ALK-positive non-small cell lung cancer. 2567 58

Colloid carcinoma is a rare subtype of lung adenocarcinoma characterized by abundant pools of extracellular mucin and scant malignant epithelium. Because of the rarity of these tumors, many of the reported clinicopathological and immunohistochemical characteristics are contradictory. Moreover, the molecular alterations that underlie these tumors are unknown. We present the clinicopathological, immunohistochemical, and molecular features of 13 cases of colloid carcinoma of the lung. The patients were 9 women and 4 men between the ages of 48 and 86 years. Surgical resection and staging were performed in all patients. Seven patients were in stage T1N0M0, 3 in T2N0M0, 2 in T2N1M0, and 1 in T2N0M1. The tumor was 100% mucinous in 9 patients, whereas in 4 cases, the lesions consisted of 50% to 90% mucin pools with the remainder being a noncolloid adenocarcinoma component ranging in morphology from bronchioalveolar to acinar, papillary, solid, or mixed patterns. Follow-up ranged from 35 to 128 months. Three patients died, 1 of disease and 2 of unrelated causes. The remaining 10 patients are alive at the time of reporting, 3 with recurrent disease. Immunohistochemical studies showed CK7, CK20, and CDX2 expression in all tumors, whereas TTF-1, surfactant A, and napsin A were not present or were only focally positive in most cases. Analysis showed KRAS mutations in 2 cases. All tumors were negative for ALK gene rearrangement and EGFR mutation. Our study highlights the clinicopathological, immunohistochemical, and molecular features of lung colloid adenocarcinoma and attempts to clarify some misconceptions regarding this rare tumor.
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PMID:An update on clinicopathological, immunohistochemical, and molecular profiles of colloid carcinoma of the lung. 2577 25

Squamous cell carcinoma of the lung (SQCCL) remains a leading cause of cancer-related death. Unlike non-smoker adenocarcinoma of the lung, where highly efficient tyrosine kinase inhibitors are available for treating mutant EGFR or ALK-rearranged, no targetable biomarkers are available for SQCCL. The frequent and focal amplification of FGFR1 has generated great expectations in offering new therapeutical options in case of 16-22% of SQCCL patients. Broad 3q chromosome amplification is widely recognized as the most common chromosomal aberration found in SQCCL, where PIK3CA, SOX2, ACK1, PRKCI, TP63, PLD1, ECT2, and others genes are located. Although SOX2 has been postulated as a key regulator of basal stem cells transformation and tumor progression, it seems to confer a good prognosis in SQCCL. It is known that each patient might carry a different length of 3q chromosome amplicon. Thus, we suggest that the number and the biological importance of the genes spanned along each patient's 3q amplicon might help to explain inter-individual outcome variations of the disease and its potential predictive value, especially when relevant oncogenes such as those mentioned above are implicated. Currently, there is no clinical predictive data available from clinical trials. In this review, we have focused on the potential role of FGFR1 in SQCCL prognosis. Additionally, we have explored recently available public data on the comprehensive genomic characterization of SQCCL, in relation to the protein-coding genes that have a strong gene copy number - mRNA correlation in 3q chromosome, that were previously described as potential driver oncogenes or its modifiers in SQCCL.
Transl Lung Cancer Res 2013 Apr
PMID:Copy number gains of FGFR1 and 3q chromosome in squamous cell carcinoma of the lung. 2580 21

Rearrangements of ROS1 and RET have been recently described as new driver mutations in lung adenocarcinoma with a frequency of about 1% each. RET and ROS1 rearrangements both represent unique molecular subsets of lung adenocarcinoma with virtually no overlap with other known driver mutations described so far in lung adenocarcinoma. Specific clinicopathologic characteristics have been described and several multitargeted receptor kinase inhibitors have shown in vitro activity against NSCLC cells harbouring these genetic alterations. In addition, the MET/ALK/ROS inhibitor crizotinib has already shown impressive clinical activity in patients with advanced ROS1-positive lung cancer. Currently, several early proof of concept clinical trials are testing various kinase inhibitors in both molecular subsets of lung adenocarcinoma patients. Most probably, personalized treatment of these genetically defined new subsets of lung adenocarcinoma will be implemented in routine clinical care of lung cancer patients in the near future.
Transl Lung Cancer Res 2013 Apr
PMID:Activated RET and ROS: two new driver mutations in lung adenocarcinoma. 2580 22

Metastatic non-small cell lung cancer (NSCLC) unfortunately remains a lethal disease, despite recent genetic characterization of subclasses of NSCLC, mainly adenocarcinoma, which has led to the development of targeted therapies that improve progression-free survival (PFS). Ultimately, however, patients fatally relapse. In this review we will focus on the search to improve survival for NSCLC patients deemed to be pan-negative for the common driver alterations susceptible to targeted therapy, above all those with EGFR mutations or ALK, ROS or RET translocations. Other uncommon driver mutations such as HER2 and BRAF mutations should be tested in order to rule out targeted treatment before assigning patients to chemotherapy. Chemotherapy yields short lived response with median survival still less than one year. Customized chemotherapy represents one way to attempt to prolong survival, although to date no prospective randomized customized studies have reported sufficient evidence to support this. In one attempt to demonstrate the role of tailoring chemotherapy, the Spanish Lung Cancer Group (SLCG) phase II customized chemotherapy trial (NCT00883480) showed that RAP80, a component of the BRCA1-A complex, influenced outcome in patients with low BRCA1 expression treated with cisplatin/gemcitabine, and in patients with intermediate/high BRCA1 levels receiving cisplatin/docetaxel or docetaxel alone. We are currently performing a prospective, randomized phase III trial comparing non-customized cisplatin/docetaxel with customized therapy in metastatic NSCLC patients (NCT00617656/GECP-BREC) and a parallel phase II study (ChiCTR-TRC-12001860) is being carried out in China (BREC-China) under the auspices of the SLCG.
Transl Lung Cancer Res 2013 Jun
PMID:Customized chemotherapy in metastatic non-small cell lung cancer (NSCLC). 2580 31


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