Clinical outcome of patients with non-small cell lung cancer receiving front-line chemotherapy according to EGFR and K-RAS mutation status

Kalikaki, Aristea; Koutsopoulos, Anastasios; Hatzidaki, Dora; Trypaki, Maria; Kontopodis, E.; Stathopoulos, Efstathios N.; Mavroudis, Dimitris; Georgoulias, Vassilis; Voutsina, Alexandra

doi:10.1016/j.lungcan.2009.09.010

Cited by 70 publications

(52 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to diagnosis in late disease stages and the poor treatment efficacy of metastatic disease, overall survival is >15% and has not improved substantially in the last 30 years (3). Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR), including gefitinib and erlotinib, have become the standard first-line therapy for patients with advanced non-small cell lung cancers (NSCLCs) harboring activating EGFR mutations (4,5). However, almost all patients eventually develop resistance to EGFR TKIs.…”

Section: Introductionmentioning

confidence: 99%

Combinations of laminin 5 with PTEN, p-EGFR and p-Akt define a group of distinct molecular subsets indicative of poor prognosis in patients with non-small cell lung cancer

Lin

Chen

et al. 2012

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Laminin 5 (Ln5) is an extracellular matrix protein that plays an important role in cell migration and tumor invasion. This study explored the expression of Ln5 and the role of its relationships with PTEN, phospho-EGFR (p-EGFR) and phospho-Akt (p-Akt) in the prognosis of patients with non-small cell lung cancer (NSCLC). The protein expression of Ln5, PTEN, p-EGFR and p-Akt was assessed by immunohistochemical analysis, and their relationships to prognosis were analyzed. IntroductionLung cancer is the leading cause of cancer-related death in the United States and throughout the world in both men and women (1,2). Due to diagnosis in late disease stages and the poor treatment efficacy of metastatic disease, overall survival is >15% and has not improved substantially in the last 30 years (3). Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR), including gefitinib and erlotinib, have become the standard first-line therapy for patients with advanced non-small cell lung cancers (NSCLCs) harboring activating EGFR mutations (4,5). However, almost all patients eventually develop resistance to EGFR TKIs.Laminin 5 (Ln5, also known as laminin 332) is an extracellular matrix (ECM) protein that plays an important role in cell migration and tumor invasion (6,7). It has a cruciform structure with one long arm and three short arms. The coiled-coil structure of the long arm is formed by three chains (α3, β3 and γ2) covalently linked via interchain disulfide bonds (8). The rod-like regions in the short arms are composed of EGF-like repeats intercalated with globular domains (9). Given the multi-domain architecture of Ln5, it seems conceivable that other receptors in addition to integrins interact with one of its many potential ligand sites to mediate its diverse cellular functions, including activation of EGFR signaling.EGFR is a key mediator of oncogenesis in NSCLCs, with its activation inducing tumor proliferation and growth, angiogenesis, invasion and metastasis, and inhibiting apoptosis (10). Activation of Akt (murine thymoma viral oncogene homolog) is one of the mechanisms that mediate the effects of EGFR (11). The Akt pathway regulates diverse biological functions (12). The tumor-suppressor gene PTEN negatively regulates the PI3K/Akt signaling pathway (13).Interactions between Ln5 and PTEN, phospho-EGFR (p-EGFR) and phospho-Akt (p-Akt) in patients with NSCLC are not well understood at the clinical level.

show abstract

Section: Introductionmentioning

confidence: 99%

Combinations of laminin 5 with PTEN, p-EGFR and p-Akt define a group of distinct molecular subsets indicative of poor prognosis in patients with non-small cell lung cancer

Lin

Chen

et al. 2012

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…doi: 10.21037/jtd.2017 View this article at: http://dx.doi.org/10.21037/jtd.2017.03.13 it also provides a specific therapeutic strategy. Tyrosine kinases inhibitors (TKIs) targeted to TK domain have been approved for the treatment of NSCLC (7,8). Several studies suggest that the application of TKIs improved response rates and progression-free survival of lung cancer patients with EGFR mutations (9,10).…”

mentioning

confidence: 99%

Clinicopathological features of Chinese lung cancer patients with epidermal growth factor receptor mutation

et al. 2017

View full text Add to dashboard Cite

Background: Epidermal growth factor receptor (EGFR) gene was the major causative gene of lung cancer and also the specific treatment target. It is necessary to analyze the genotype and phenotype characters of patients. Methods: We investigated 1,034 lung cancer patients in this study. The collected clinicopathological parameters included gender, age at diagnosis, smoking status, pathological TNM stage, tumor morphology and location, visceral pleural invasion as well as histological type. Results: Almost 50% participants had EGFR mutations. L858R in exon 21 was the most common type.Concomitant mutation, 19 del and L858R, were detected in 20 patients. Compared to patients with exon 19 del or L858R mutations solely, they were inclined to have small size adenocarcinomas which occurred in bilateral and invaded the visceral pleura. The tyrosine kinases inhibitors (TKIs)-resistant mutation, insertions in exon 20, was detected in 11 patients. Conclusions: The summarized clinicopathological features will help clinicians to implement the feasible treatment plan.Keywords: Lung cancer; epidermal growth factor receptor (EGFR) gene; mutation; phenotype; genotype Submitted Jan 14, 2017. Accepted for publication Feb 16, 2017Feb 16, . doi: 10.21037/jtd.2017 View this article at: http://dx.doi.org/10.21037/jtd.2017.03.13 it also provides a specific therapeutic strategy. Tyrosine kinases inhibitors (TKIs) targeted to TK domain have been approved for the treatment of NSCLC (7,8). Several studies suggest that the application of TKIs improved response rates and progression-free survival of lung cancer patients with EGFR mutations (9,10). The sensitivity of lung cancer patients to TKIs is associated with the mutation type. Patients with deletions in exon 19 and L858R in exon 21 responded positively. In this respect, the detection of EGFR mutations is the premise to the treatment of lung cancer patients. But in clinic the quantity of biopsy samples were not enough to fulfill the entire mutation screening. The phenotypic traits summary could help clinicians make judgement beforehand. Furthermore, most previous studies on EGFR mutations mainly focused on lung adenocarcinoma, few studies have evaluated the EGFR mutations in other lung cancer type in large scale. In the current study, we analyzed the EGFR mutation spectrum in Chinese lung cancer patients and summarized the clinicopathological characters of patients with EGFR gene mutations. Methods Ethical approvalThis study was approved by the Institutional Review Board (IRB) of Shanghai Pulmonary Hospital affiliated Tongji University (No. 2014-016). Written informed consents were obtained from all participants. The methods were carried out in accordance with the approved guidelines. Patients and specimen collectionThe consecutive primary lung cancer patients who were admitted into the Shanghai Pulmonary Hospital affiliated Tongji University from Jun. 2014 to Oct. 2015 were recruited. No choose or correct was performed on patients' collection. None of these patients received any antican...

show abstract

“…In EGFR-mutant cases, EGFR-TKIs would be expected to be effective and long-term survival could be expected with local treatment of cases of localized recurrence, such as cases 3 and 6 in Table VI. Our study demonstrated that bilateral/contralateral lung recurrence was significantly more frequent among EGFR+ cases. In those cases, long-term survival may be achieved with combination therapy, consisting of EGFR-TKI treatment, cytotoxic chemotherapy and local treatment, for each lesion (21)(22)(23)(24). In general, long post-recurrence survival may be expected in patients with slow-growing tumors or long recurrence-free survival; however, no association between post-recurrence survival time and recurrence-free survival time according to EGFR mutations was observed in this study.…”

Section: Discussionmentioning

confidence: 59%

Postrecurrence survival of surgically resected pulmonary adenocarcinoma patients according to EGFR and KRAS mutation status

Ohtaki

Shimizu

Kakegawa

et al. 2013

Molecular and Clinical Oncology

View full text Add to dashboard Cite

Abstract. The aim of this study was to investigate the prognosis of pulmonary adenocarcinoma patients following postoperative recurrence, according to epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) gene mutation status and recurrence site. In total 58 adenocarcinoma patients with recurrence following surgical resection were retrospectively evaluated between 2002 and 2011. The patients were divided into groups according to the presence or absence of EGFR and KRAS mutations and the clinicopathological characteristics, recurrence sites and postrecurrence survival were compared. EGFR and KRAS mutations were detected in 26 (45%) and 11 patients (19%), respectively. Initial recurrence was distant in 25 (43%), local in 17 (29%) and both distant and local in 16 cases (28%). In EGFR-mutant (EGFR+) cases, bilateral/contralateral lung recurrence was a frequent finding. EGFR+ cases exhibited significantly better outcomes compared to KRAS+ and EGFR-KRAS-(wild-type) cases. The 2-year post-recurrence survival rates were 81, 18 and 47% in EGFR+, KRAS+ and wild-type cases, respectively. The patients with distant organ recurrence exhibited significantly worse survival compared with those without distant recurrence in wild-type, but not in the EGFR+ cases or the entire cohort. Multivariate analysis revealed that EGFR mutations and a number of recurrent lesions were the only statistically significant independent predictors of postrecurrence prognosis. Our results indicated distinct survival differences in recurrent adenocarcinoma patients according to driver mutations. Patients with EGFR-mutated tumors exhibited increased survival, regardless of recurrence at distant sites, whereas patients with KRAS-mutated adenocarcinoma exhibited poor outcome following postoperative recurrence. Therefore, the assessment of driver mutations is essential for predicting postrecurrence survival following surgical resection.

show abstract

Clinical outcome of patients with non-small cell lung cancer receiving front-line chemotherapy according to EGFR and K-RAS mutation status

Cited by 70 publications

References 32 publications

Combinations of laminin 5 with PTEN, p-EGFR and p-Akt define a group of distinct molecular subsets indicative of poor prognosis in patients with non-small cell lung cancer

Combinations of laminin 5 with PTEN, p-EGFR and p-Akt define a group of distinct molecular subsets indicative of poor prognosis in patients with non-small cell lung cancer

Clinicopathological features of Chinese lung cancer patients with epidermal growth factor receptor mutation

Postrecurrence survival of surgically resected pulmonary adenocarcinoma patients according to EGFR and KRAS mutation status

Contact Info

Product

Resources

About