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New era of epidermal growth factor receptor-tyrosine kinase inhibitors for lung cancer
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作者 Joana Espiga Macedo 《World Journal of Respirology》 2016年第2期57-62,共6页
Lung cancer is the leading cause of death globally, besides recent advances in its management; it maintains a low 5-year survival rate of 15%. The discovery of epidermal growth factor receptor(EGFR) activating mutatio... Lung cancer is the leading cause of death globally, besides recent advances in its management; it maintains a low 5-year survival rate of 15%. The discovery of epidermal growth factor receptor(EGFR) activating mutations and the introduction of its tyrosine kinase inhibitors(TKIs) have expanded the treatment options for patients with non-small cell lung cancer. Nowadays, EGFR mutation testing is now a common routine for newly diagnosed lung cancer. First generation TKIs developed, erlotinib and gefitinib, were reversible ones. After a median of 14 mo, eventually all EGFR mutated patients develop resistance to reversible TKIs. Afatinib, dacomitinib and neratinib, second generation inhibitors, are selective and irreversible TKIs. Finally, third generation phase Ⅰclinical trials were performed, with lower toxicity profiles, and targeting with more precision the driving clone of this heterogeneous disease. 展开更多
关键词 EPIDERMAL growth factor receptor-tyrosine kinase inhibitors CLONAL evolution NON-SMALL cell lung cancer ACQUIRED resistance
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Research progress in the use of combinations of platinum-based chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors
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作者 Chi Pan Suzhan Zhang Jianjin Huang 《The Chinese-German Journal of Clinical Oncology》 CAS 2013年第3期133-136,共4页
In the past decade,the advent of the epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)has dramatically influenced the therapeutic strategies for treating lung cancer,but with tumor progression and... In the past decade,the advent of the epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)has dramatically influenced the therapeutic strategies for treating lung cancer,but with tumor progression and drug resistance,patients will ultimately develop reduced sensitivity to EGFR-TKIs.How can we delay the emergence of drug resistance? What is the next strategy after drug resistance? How to reasonably combine platinum-based chemotherapy and EGFR-TKIs? These questions are currently the focus of lung cancer research.Clinical studies have reported that platinum-based chemotherapy can increase the sensitivity to EGFR-TKIs.However,results of pre-clinical and clinical studies have been inconsistent.The mechanisms of platinum chemotherapy and EGFR-TKIs are still unknown due to the lack of systematic research.Therefore,systematic studies are required to show the mechanisms of EGFR-TKIs and chemotherapy agents and define the markers sensitive to their combinations when given concurrently or sequentially. 展开更多
关键词 platinum-based chemotherapy epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) gefi-tinib: erlotinib
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Rapid mitogen-activated protein kinase activation by transforming growth factor α in wounded rat intestinal epithelial cells 被引量:14
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作者 Michael Gke, Michiyuki Kanai, Kathryn Lynch Devaney, and Daniel K. Podolsky Gastrointestinal Unit, Department of Medicine, and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massa 《World Journal of Gastroenterology》 SCIE CAS CSCD 1998年第3期83-83,共1页
AIM To define signaling events initiating healing after intestinal epithelial injury, activation of mitogen activated protein kinase (MAPK) pathways was assessed after wounding using an in vitro model. METHODS P... AIM To define signaling events initiating healing after intestinal epithelial injury, activation of mitogen activated protein kinase (MAPK) pathways was assessed after wounding using an in vitro model. METHODS Proteins isolated from wounded monolayers of nontransformed intestinal epithelial cells (IEC 6) were analyzed for tyrosine phosphorylation and MAPK expression by Western blot. Extracellular signal regulated kinase (ERK) 1, ERK2, and Raf 1 activities were assessed by immune complex kinase assays. RESULTS Tyrosine phosphorylation of several proteins including ERK1 was substantially increased 5 minutes after injury. Another MAPK, c Jun N terminal protein kinase (JNK), was also activated after wounding. Conditioned medium from wounded but not intact IEC 6 monolayers resulted in increased activity of ERK1, ERK2, and Raf 1 kinase. Wound conditioned medium stimulated proliferation of subconfluent IEC 6 cells compared with conditioned medium from intact IEC 6 cultures and contained higher amounts of transforming growth factor (TGF) α than supernatants of confluent IEC 6 cultures. Activation of ERK1 and ERK2 was partially inhibited by neutralizing anti TGF α. CONCLUSION Wounding of intestinal epithelial cells results in activation of Raf 1, ERK1, ERK2, and JNK1 MAPKs and subsequent cell proliferation in vitro. Activation of ERK1 and ERK2 is mediated in part by TGF α. 展开更多
关键词 INTESTINAL mitogen ACTIVATION by cells epithelial factor growth RAPID kinase
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Epidermal growth factor receptor tyrosine kinase inhibitors for non-small cell lung cancer 被引量:5
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作者 Kazuhiro Asami Shinji Atagi 《World Journal of Clinical Oncology》 CAS 2014年第4期646-659,共14页
First-generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs), including gefitinib and erlotinib, have proven to be highly effective agents for advanced non-small cell lung cancer(NSCLC) in p... First-generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs), including gefitinib and erlotinib, have proven to be highly effective agents for advanced non-small cell lung cancer(NSCLC) in patients harboring an activating EGFR mutation such as the exon 19 deletion mutation and L858 R. Although those reversible small molecular targeted agents provide a significant response and survival benefit, all responders eventually acquire resistance. Secondgeneration EGFR-targeting agents, such as irreversible EGFR/HER2 tyrosine kinase inhibitors and pan-HER TKIs, may improve survival further and be useful for patients who acquired resistance to first-generation EGFR-TKIs. This review discusses novel therapeutic strategies for EGFR-mutated advanced NSCLC using first- and second-generation EGFR-TKIs. 展开更多
关键词 EPIDERMAL growth factor RECEPTOR mutation EPIDERMAL growth factor RECEPTOR TYROSINE kinase inhibitors NON-SMALL cell lung cancer Secondary resistance
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Is there a role for epidermal growth factor receptor tyrosine kinase inhibitors in epidermal growth factor receptor wildtype non-small cell lung cancer?
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作者 Edurne Arriola lvaro Taus David Casadevall 《World Journal of Clinical Oncology》 CAS 2015年第4期45-56,共12页
Non-small cell lung cancer(NSCLC) is the most common type of lung cancer with a world-wide annual incidence of around 1.3 million. The majority of patients arediagnosed with advanced disease and survival remains poor.... Non-small cell lung cancer(NSCLC) is the most common type of lung cancer with a world-wide annual incidence of around 1.3 million. The majority of patients arediagnosed with advanced disease and survival remains poor. However, relevant advances have occurred in recent years through the identification of biomarkers that predict for benefit of therapeutic agents. This is exemplified by the efficacy of epidermal growth factor receptor(EGFR) tyrosine kinase inhibitors for the treatment of EGFR mutant patients. These drugs have also shown efficacy in unselected populations but this point remains controversial. Here we have reviewed the clinical data that demonstrate a small but consistent subgroup of EGFR wild-type patients with NSCLC that obtain a clinical benefit from these drugs. Moreover, we review the biological rationale that may explain this benefit observed in the clinical setting. 展开更多
关键词 NON-SMALL cell lung cancer TYROSINE kinase inhibitors EPIDERMAL growth factor RECEPTORS
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Advanced Lung Adenocarcinoma with EGFR 19-del Mutation Transformed into SCC after EGFR-tyrosine Kinase inhibitors Treatment:A Case report 被引量:1
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作者 Xing-Zu Ji Zhong-Da Liu +4 位作者 Yi-Ping Ye Quan Li Xiao-Jing Liu Min-Hua Zhou Yi Jin 《World Journal of Clinical Cases》 SCIE 2024年第20期4405-4411,共7页
BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)significantly improve the survival of patients with Epidermal growth factor receptor(EGFR)sensitive mutations in non-small cell lung can... BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)significantly improve the survival of patients with Epidermal growth factor receptor(EGFR)sensitive mutations in non-small cell lung cancer(NSCLC).CASE SUMMARY A 67-year-old female patient in advanced lung adenocarcinoma suffered from drug resistance after EGFR-TKIs treatment.Secondary pathological tissue biopsy confirmed squamous cell carcinoma(SCC)transformation.Patients inevitably encountered drug resistance issues after receiving EGFR-TKIs treatment for a certain period of time,while EGFR-TKIs can significantly improve the survival of patients with EGFR-sensitive mutations in NSCLC.Notably,EGFR-TKIs resistance includes primary and acquired.Pathological transformation is one of the mechanisms of acquired resistance in EGFR-TKIs,with SCC transformation being relatively rare.Our results provide more detailed results of the patient’s diagnosis and treatment process on SCC transformation after EGFR-TKIs treatment for lung adenocarcinoma.CONCLUSION Squamous cell carcinoma transformation is one of the acquired resistance mechanisms of EGFR-TKIs in advanced lung adenocarcinoma with EGFR mutations. 展开更多
关键词 Lung adenocarcinoma Squamous cell carcinoma Pathological histological transformation Epidermal growth factor receptor tyrosine kinase inhibitors Drug resistance Case report
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Tyrosine kinase inhibitors and human epidermal growth factor receptor-2 positive breast cancer
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作者 Aya Abunada Zaid Sirhan +1 位作者 Anita Thyagarajan Ravi P Sahu 《World Journal of Clinical Oncology》 CAS 2023年第5期198-202,共5页
The body of evidence investigating human epidermal growth factor receptor-2(HER2)directed therapy in patients with breast cancer(BC)has been growing within the last decade.Recently,the use of tyrosine kinase inhibitor... The body of evidence investigating human epidermal growth factor receptor-2(HER2)directed therapy in patients with breast cancer(BC)has been growing within the last decade.Recently,the use of tyrosine kinase inhibitors(TKIs)has been of particular interest in the treatment of human malignancies.This literature commentary is intended to highlight the most recent findings associated with the widely-studied TKI agents and their clinical significance in improving the outcomes of HER2 positive BC. 展开更多
关键词 Human epidermal growth factor receptor-2 positive breast cancer Tyrosine kinase inhibitors LAPATINIB Pyrotinib Tucatinib TRASTUZUMAB
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Therapeutic Effect of First-line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI)Combined with Whole Brain Radiotherapy on Patients with EGFR Mutation-positive Lung Adenocarcinoma and Brain Metastases 被引量:1
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作者 Shao-bo KE Hu QIU +2 位作者 Jia-mei CHEN Wei SHI Yong-shun CHEN 《Current Medical Science》 SCIE CAS 2018年第6期1062-1068,共7页
This study compared the therapeutic effect of first-line epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)with that of EGFR-TKI plus whole brain radiotherapy(WBRT)on patients with EGFR mutation-posi... This study compared the therapeutic effect of first-line epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)with that of EGFR-TKI plus whole brain radiotherapy(WBRT)on patients with EGFR mutation-positive lung adenocarcinoma and brain metastases.A total of 139 patients with lung adenocarcinoma and brain metastases treated with first-line EGFR-TK1therapy from September 2008 to December 2017 were enrolled in this study.The study endpoints were intracranial time to progression(TTP)and overall survival(OS).The effects of clinical pathological parameters and EGFR gene status on the study endpoints were compared.The results showed that the intracranial TTP was significantly longer in EGFR-TKI plus WBRT group than in EGFR-TKI group (median 30.0 vs.18.2 months,χ2=10.824,P=0.001),but no significant difference in the OS was noted between the two groups (median 48.0 vs.41.1 months,χ2=0.012, P=0.912).Also,there was no statistically significant difference in the OS between patients treated with early and late radiotherapy (P=0.849)and between those with asymptomatic and those with symptomatic intracranial metastases (P=0.189).The OS and intracranial TTP of patients with intracranial oligometastases (≤3metastatic sites)were not significantly different from those of patients with multiple intracranial metastases (P=0.104 and P=0.357,respectively),and exon 19 and exon 21 mutations didn't show significant effects on the OS and intracranial TTP of patients (P=0.418 and P=0.386,respectively).In conclusion,there was no statistically significant difference in the OS between the EGFR-TKI alone group and EGFR-TK1 plus WBRT group.However, simultaneous use of WBRT was found to significantly prolong intracranial TTP and improve cerebral symptoms,and thus EGFR-TKI and WBRT combined may be clinically beneficial for patients with EGFR mutation-positive lung adenocarcinoma and brain metastases. 展开更多
关键词 lung ADENOCARCINOMA BRAIN METASTASES EPIDERMAL growth factor receptor TYROSINE kinase inhibitor whole BRAIN radiotherapy
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Advanced lung adenocarcinoma with EGFR 19-del mutation transforms into squamous cell carcinoma after EGFR tyrosine kinase inhibitor treatment
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作者 Ruo-Bing Qi Zheng-Hao Wu 《World Journal of Clinical Cases》 SCIE 2024年第32期6543-6546,共4页
In this editorial we comment on the article by Ji et al.We focus specifically on the EGFR tyrosine kinase inhibitor(EGFR-TKI)treatment and the development of drug resistance to EGFR-TKIs.
关键词 Lung adenocarcinoma Squamous cell carcinoma Histological transformation Epidermal growth factor receptor tyrosine kinase inhibitor Drug resistance
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Effects of retinoic acid on proliferation,phenotype and expression of cyclin-dependent kinase inhibitors in TGF-β1-stimulated rat hepatic stellate cells 被引量:23
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作者 Guang Cun Huang Jin Sheng Zhang Yue E Zhang Department of Pathology School of Basic Medical Sciences,Fudan University.Shanghai 200032,China 《World Journal of Gastroenterology》 SCIE CAS CSCD 2000年第6期819-823,共5页
AIM To study the molecular mechanisms ofretinoic acid(RA)on proliferation andexpression of cyclin-dependent kinase inhibitors(CKI),i.e.p16,p21 and p27 in cultured rathepatic stellate cells(HSC)stimulated withtransform... AIM To study the molecular mechanisms ofretinoic acid(RA)on proliferation andexpression of cyclin-dependent kinase inhibitors(CKI),i.e.p16,p21 and p27 in cultured rathepatic stellate cells(HSC)stimulated withtransforming growth factor beta 1(TGF-β1).METHODS HSC were isolated from healthy ratlivers and cultured.After stimulated with1 mg/L TGF-β1,subcultured HSC were treatedwith or without 1 nmol/L RA.MTT assay,immunocytochemistry(ICC)for p16,p21,p27and α-smooth muscle actin(α-SMA)protein,insitu hybridization(ISH)for retinoic acidreceptor beta 2(RAR-β2)and p16,p21 and p27mRNA and quantitative image analysis(partially)were performed.RESULTS RA inhibited HSC proliferation(41.50%,P【0.05),decreased the protein levelof α-SMA(55.09%,P【0.05),and induced HSCto express RAR-β2 mRNA.In addition,RAincreased the protein level of p16(218.75%,P【0.05)and induced p21 protein expression;meanwhile,p27 was undetectable by ICC in bothcontrol and RA-treated HSC.However,RA hadno influence on the mRNA levels of p16,p21 orp27 as determined by ISH.CONCLISION Up-regulation of p16 and p21 on post-transcriptional level may contribule, in part to RA inhibition of TGF-β1-initiated rat HSC activation in vitro. 展开更多
关键词 RETINOIC acid cyclindependent kinase inhibitor hepatic stellate CELL CELL culture TRANSFORMING growth factor beta 1 liver FIBROSIS
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Treatment of gastrointestinal neuroendocrine tumors with inhibitors of growth factor receptors and their signaling pathways: Recent advances and future perspectives 被引量:4
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作者 Michael Hpfner Detlef Schuppan Hans Scherübl 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第16期2461-2473,共13页
The limited efficacy of conventional cytotoxic treatment regimes for advanced gastrointestinal neuroendocrine cancers emphasizes the need for novel and more effective medical treatment options. Recent findings on the ... The limited efficacy of conventional cytotoxic treatment regimes for advanced gastrointestinal neuroendocrine cancers emphasizes the need for novel and more effective medical treatment options. Recent findings on the specific biological features of this family of neoplasms has led to the development of new targeted therapies, which take into account the high vascularization and abundant expression of specific growth factors and cognate tyrosine kinase receptors. This review will briefly summarize the status and future perspectives of antiangiogenic, mTOR- or growth factor receptor-based pharmacological approaches for the innovative treatment of gastrointestinal neuroendocrine tumors. In view of the multitude of novel targeted approaches, the rationale for innovative combination therapies, i.e. combining growth factor (receptor)-targeting agents with chemo- or biotherapeutics or with other novel anticancer drugs such as HDAC or proteasome inhibitors will be taken into account. 展开更多
关键词 growth factor receptor Neuroendocrinegastrointestinal tumor Small molecule inhibitor lonoclonal antibody Multi kinase inhibition
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Tyrosine kinase inhibitors:Multi-targeted or single-targeted? 被引量:2
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作者 Fleur Broekman Elisa Giovannetti Godefridus J Peters 《World Journal of Clinical Oncology》 CAS 2011年第2期80-93,共14页
Since in most tumors multiple signaling pathways are involved,many of the inhibitors in clinical development are designed to affect a wide range of targeted kinases.The most important tyrosine kinase families in the d... Since in most tumors multiple signaling pathways are involved,many of the inhibitors in clinical development are designed to affect a wide range of targeted kinases.The most important tyrosine kinase families in the development of tyrosine kinase inhibitors are the ABL,SCR,platelet derived growth factor,vascular endothelial growth factor receptor and epidermal growth factor receptor families.Both multi-kinase inhibitors and singlekinase inhibitors have advantages and disadvantages,which are related to potential resistance mechanisms,pharmacokinetics,selectivity and tumor environment.In different malignancies various tyrosine kinases are mutated or overexpressed and several resistance mechanisms exist.Pharmacokinetics is influenced by interindividual differences and differs for two single targeted inhibitors or between patients treated by the same tyrosine kinase inhibitor.Different tyrosine kinase inhibitors have various mechanisms to achieve selectivity,while differences in gene expression exist between tumor and stromal cells.Considering these aspects,one type of inhibitor can generally not be preferred above the other,but will depend on the specific genetic constitution of the patient and the tumor,allowing personalized therapy.The most effective way of cancer treatment by using tyrosine kinase inhibitors is to consider each patient/tumor individually and to determine the strategy that specifically targets the consequences of altered(epi)genetics of the tumor.This strategy might result in treatment by a single multi kinase inhibitor for one patient,but in treatment by a couple of single kinase inhibitors for other patients. 展开更多
关键词 Tyrosine kinase inhibitors TARGETED therapy Epidermal growth factor RECEPTOR Vascular endothelial growth factor RECEPTOR Platelet derived growth factor BREAKPOINT cluster region-Abelson murine leukemia oncogene homolog 1 Janus kinase
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Repurposed anti-cancer epidermal growth factor receptor inhibitors: mechanisms of neuroprotective effects in Alzheimer’s disease 被引量:2
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作者 Heba M.Mansour Hala M.Fawzy +1 位作者 Aiman S.El-Khatib Mahmoud M.Khattab 《Neural Regeneration Research》 SCIE CAS CSCD 2022年第9期1913-1918,共6页
Numerous molecular mechanisms are being examined in an attempt to discover disease-modifying drugs to slow down the underlying neurodegeneration in Alzheimer’s disease.Recent studies have shown the beneficial effects... Numerous molecular mechanisms are being examined in an attempt to discover disease-modifying drugs to slow down the underlying neurodegeneration in Alzheimer’s disease.Recent studies have shown the beneficial effects of epidermal growth factor receptor inhibitors on the enhancement of behavioral and pathological sequelae in Alzheimer’s disease.Despite the promising effects of epidermal growth factor receptor inhibitors in Alzheimer’s disease,there is no irrefutable neuroprotective evidence in well-established animal models using epidermal growth factor receptor inhibitors due to many un-explored downstream signaling pathways.This caused controversy about the potential involvement of epidermal growth factor receptor inhibitors in any prospective clinical trial.In this review,the mystery beyond the under-investigation of epidermal growth factor receptor in Alzheimer’s disease will be discussed.Furthermore,their molecular mechanisms in neurodegeneration will be explained.Also,we will shed light on SARS-COVID-19 induced neurological manifestations mediated by epidermal growth factor modulation.Finally,we will discuss future perspectives and under-examined epidermal growth factor receptor downstream signaling pathways that warrant more exploration.We conclude that epidermal growth factor receptor inhibitors are novel effective therapeutic approaches that require further research in attempts to be repositioned in the delay of Alzheimer’s disease progression. 展开更多
关键词 Alzheimer’s disease AUTOPHAGY drug re-positioning epidermal growth factor receptor human epidermal growth factor receptor-2 neurodegenerative diseases NEUROINFLAMMATION oxidative stress tyrosine kinase inhibitors
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Efficacy of EGFR Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancer Patients Harboring Different Types of EGFR Mutations:A Retrospective Analysis 被引量:8
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作者 刘华丽 韩光 +5 位作者 彭敏 翁一鸣 袁静萍 杨桂芳 于金明 宋启斌 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2017年第6期864-872,共9页
With the development of molecular pathology, many types of epidermal growth factor receptor(EGFR) mutations have been identified. The efficacy of EGFR tyrosine kinase inhibitors(EGFR-TKIs) in non-small cell lung c... With the development of molecular pathology, many types of epidermal growth factor receptor(EGFR) mutations have been identified. The efficacy of EGFR tyrosine kinase inhibitors(EGFR-TKIs) in non-small cell lung cancer(NSCLC) patients with different types of EGFR mutations, especially in patients with single rare mutations or complex mutations(co-occurrence of two or more different mutations), has not been fully understood. This study aimed to examine the efficacy of EGFR-TKIs in NSCLC patients with different types of EGFR mutations. Clinical data of 809 NSCLC patients who harbored different types of EGFR mutations and treated from January 2012 to October 2016 at Renmin Hospital and Zhongnan Hospital, Wuhan, were retrospectively reviewed. The clinical characteristics of these patients and the efficacy of EGFR-TKIs were analyzed. Among these patients, 377 patients had only the EGFR del-19 mutation, 362 patients the EGFR L858R mutation in exon 21, 33 patients single rare mutations and 37 patients complex mutations. Among these 809 patients, 239 patients were treated with EGFR-TKIs. In all the 239 patients, the disease control rate(DCR) was 93.7% with two patients(0.2%) achieving complete response(CR), the median progression free survival(PFS) was 13.0 months(95% confidence interval [CI], 11.6–14.4 months), and the median overall survival(OS) was 55.0 months(95% CI, 26.3–83.7 months). Subgroup analysis revealed that the DCR in patients harboring single rare or complex mutations of EGFR was significantly lower than in those with del-19 or L858 R mutation(P〈0.001). Patients with classic mutations(del-19 and/or L858 R mutations) demonstrated longer PFS(P〈0.001) and OS(P=0.017) than those with uncommon mutations(single rare and/or complex mutations). Furthermore, the patients with single rare mutations had shorter median OS than in those with other mutations. Multivariate Cox regression analysis identified that the type of EGFR mutations was an independent risk factor for PFS(hazard ratio [HR]=0.308, 95% CI, 0.191–0.494, P〈0.001) and OS(HR=0.221, 95% CI, 0.101–0.480, P〈0.001). The results suggest that the single rare or complex EGFR mutations confer inferior efficacy of EGFR-TKIs treatment to the classic mutations. The prognosis of the single rare EGFR mutations is depressing. EGFR-TKIs may be not a good choice for NSCLC patients with single rare mutations of EGFR. Further studies in these patients with uncommon mutations(especially for the patients with single rare mutations) are needed to determine a better precision treatment. 展开更多
关键词 non-small cell lung cancer epidermal growth factor receptor rare mutations complex mutations tyrosine kinase inhibitors
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Coexistence of anaplastic lymphoma kinase rearrangement in lung adenocarcinoma harbouring epidermal growth factor receptor mutation:A single-center study 被引量:1
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作者 Wei-Xiang Zhong Xi-Feng Wei 《World Journal of Clinical Cases》 SCIE 2022年第33期12164-12174,共11页
BACKGROUND Accumulating evidences confirm that epidermal growth factor receptor(EGFR)mutation and anaplastic lymphoma kinase(ALK)rearrangement have coexisted in lung adenocarcinoma(LUAD).However,Its biological mechani... BACKGROUND Accumulating evidences confirm that epidermal growth factor receptor(EGFR)mutation and anaplastic lymphoma kinase(ALK)rearrangement have coexisted in lung adenocarcinoma(LUAD).However,Its biological mechanism,clinicopathological features,and optimization of targeted drugs have not yet been completely elucidated.AIM To explore the clinical profile of LUAD patients with co-mutations of EGFR and ALK genes,with hopes of scientifically guiding similar patients towards selected,targeted drugs.METHODS Two hundred and thirty-seven LUAD patients were enrolled.EGFR mutations were detected by the amplification refractory mutation system-peptide nucleic acid technique,while the expression of ALK rearrangement was screened by the 5′/3′imbalance strategy for reverse transcription followed by quantitative polymerase chain reaction analysis.The clinicopathological features of these patients were analysed retrospectively,and the follow-up data were collected.RESULTS There were six cases with co-mutations of EGFR and ALK genes,which were more common in women,non-smoking and stage IV LUAD patients with bone metastasis,hence a positive rate of 2.53%(6/237).EGFR-tyrosine kinase inhibitors(EGFR-TKIs)were their preferred drugs for targeted therapy in these patients,with progression-free survival ranging from two months to six months.CONCLUSION In Gannan region,the positive rate of co-mutations of EGFR and ALK genes in LUAD patients is relatively high,and the co-mutations are more common in women,non-smoking and stage IV patients with bone metastasis.These patients prefer EGFR-TKIs as their preferred targeted drugs,but the therapeutic effect is not good.EGFR/ALK dual-TKIs may be more effective targeted drugs,which needs further study. 展开更多
关键词 Lung adenocarcinoma Epidermal growth factor receptor mutation Anaplastic lymphoma kinase rearrangement Co-mutation Tyrosine kinase inhibitor
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Role of Connective Tissue Growth Factor in Extracellular Matrix Degradation in Renal Tubular Epithelial Cells 被引量:4
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作者 张春 朱忠华 +3 位作者 刘建社 杨晓 付玲 邓安国 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2007年第1期44-47,共4页
In order to investigate the effects of connective tissue growth factor (CTGF) antisense oligodeoxynucleotide (ODN) on plasminogen activator inhibitor-1 (PAI-1) expression in renal tubular cells induced by transf... In order to investigate the effects of connective tissue growth factor (CTGF) antisense oligodeoxynucleotide (ODN) on plasminogen activator inhibitor-1 (PAI-1) expression in renal tubular cells induced by transforming growth factor β1 (TGF-β1) and to explore the role of CTGF in the degradation of renal extracellular matrix (ECM), a human proximal tubular epithelial cell line (HKC) was cultured in vitro. Cationic lipid-mediated CTGF antisense ODN was transfected into HKC. After HKC were stimulated with TGF-β1 (5 μg/L), the mRNA level of PAI-1 was detected by RT-PCR. Intracellular PAI-1 protein synthesis was assessed by flow cytometry. The secreted PAI-1 in the media was determined by Western blot. The results showed that TGF-β1 could induce tubular CTGF and PAI-1 mRNA expression. The PAI-1 mRNA expression induced by TGF-β1 was significantly inhibited by CTGF antisense ODN. CTGF antisense ODN also inhibited intracellular PAI-1 protein synthesis and lowered the levels of PAI-1 protein secreted into the media. It was concluded that CTGF might play a crucial role in the degradation of excessive ECM during tubulointerstitial fibrosis, and blocking the biological effect of CTGF may he a novel way in preventing renal fibrosis. 展开更多
关键词 connective tissue growth factor antisense oligodeoxynucleotide plasminogen activator inhibitor-1 renal tubular epithelial cells
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Epidermal growth factor receptor inhibitors in colorectal cancer treatment: What's new?
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作者 M Ponz-Sarvisé J Rodríguez +4 位作者 A Viudez A Chopitea A Calvo J García-Foncillas I Gil-Bazo 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第44期5877-5887,共11页
Colorectal cancer constitutes one of the most common malignancies and the second leading cause of death from cancer in the western world representing one million new cases and half a million deaths annually worldwide.... Colorectal cancer constitutes one of the most common malignancies and the second leading cause of death from cancer in the western world representing one million new cases and half a million deaths annually worldwide. The treatment of patients with metastatic colon cancer comprises different regimens of chemotherapeutic compounds (fluoropyrimidines, irinotecan and oxaliplatin) and new targeted therapies. Interestingly, most recent trials that attempt to expose patients to all five-drug classes (fluoropyrimidines, irinotecan, oxaliplatin, bevacizumab and cetuximab) achieve an overall survival well over 2 years. In this review we will focus on the main epidermal growth factor receptor inhibitors demonstrating clinical benefit for colorectal cancer mainly cetuximab, panitumumab, erlotinib and gefltinib. We will also describe briefly the molecular steps that lie beneath them and the different clinical or molecular mechanisms that are reported for resistance and response. 展开更多
关键词 Epidermal growth factor receptor inhibitors CETUXIMAB PANITUMUMAB ERLOTINIB GEFITINIB Metastatic colorectal cancer Tyrosine kinase inhibitors Monoclonal antibodies
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Management of tyrosine kinase inhibitor resistance in lung cancer with EGFR mutation 被引量:2
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作者 Kevin Becker Yiqing Xu 《World Journal of Clinical Oncology》 CAS 2014年第4期560-567,共8页
The identification of driver mutations and drugs that inhibit their activity has been a major therapeutic advance for patients with advanced lung adenocarcinoma. Unfortunately, the success of these drugs is limited by... The identification of driver mutations and drugs that inhibit their activity has been a major therapeutic advance for patients with advanced lung adenocarcinoma. Unfortunately, the success of these drugs is limited by the universal development of resistance. Treatment failure can result from inadequate drug exposure or selection of resistant malignant clones. Clinically distinct mechanisms of disease progression have been identified and can inform treatment decisions. Investigations into the biochemical mechanisms of tyrosine kinase inhibitor resistance may provide additional therapeutic targets by which the efficacy of targeted therapy can be improved. 展开更多
关键词 EPIDERMAL growth factor receptor mutation TYROSINE kinase inhibitor Lung cancer ADENOCARCINOMA RESISTANCE Targeted therapy
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Clinical Benefit of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors Plus Radiotherapy for Epidermal Growth Factor Receptor-Mutated Metastatic Non-Small Cell Lung Cancer: A Retrospective Analysis on Real World Data 被引量:2
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作者 Wang Ranlin Li Tao +2 位作者 Lv Jiahua Sun Chang Shi Qiuling 《肿瘤预防与治疗》 2019年第5期385-394,共10页
Objective: To investigate the benefit of epidermal growth factor receptor( EGFR) tyrosine kinase inhibitors( TKIs)with radiotherapy in patients with EGFR mutation-positive metastatic non-small cell lung cancer( NSCLC)... Objective: To investigate the benefit of epidermal growth factor receptor( EGFR) tyrosine kinase inhibitors( TKIs)with radiotherapy in patients with EGFR mutation-positive metastatic non-small cell lung cancer( NSCLC),compared with TKIs alone.Methods: A total of 103 patients with stage Ⅳ EGFR-mutated NSCLC treated from February 2015 to May 2017 at Sichuan Cancer Hospital were analyzed retrospectively. Fifty patients were treated with EGFR-TKIs( gefitinib or erlotinib) plus radiotherapy( the TKI +RT group) and 53 patients received EGFR-TKIs alone( the TKI group). Tumor response,survival and toxicities were compared between the two groups. Results: Median follow-up time was 11. 7 months( 2. 8-36. 3 months). The overall response rate( ORR) and disease control rate( DCR) in the TKI + RT group vs the TKI group were 62% vs 37. 7%( P = 0. 014) and 88% vs 75. 5%( P =0. 101),respectively. The median progression-free survival( PFS) and median overall survival( OS) in the TKI + RT group were superior to those of the TKI group( 18. 87 months vs 12. 80 months,P = 0. 035 and 23. 10 months vs 18. 30 months,P = 0. 011). OS rates in the TKI + RT group and the TKI group were 56. 0% vs 35. 8% at year 1( P = 0. 04) and 16. 0% vs 3. 8% at year 2( P =0. 036). Multivariate Cox model found that TKI + RT related to significantly better OS( hazard ratio = 0. 209;95% CI,0. 066 to0. 661;P = 0. 008) than TKI alone. Adverse events did not differ significantly between the two groups( P > 0. 050). Conclusion:Compared with EGFR-TKIs alone,EGFR-TKIs combined with radiotherapy was well tolerated and showed benefit in tumor response and survival for EGFR mutation-positive metastatic NSCLC patients. 展开更多
关键词 RADIOTHERAPY NON-SMALL cell lung cancer EPIDERMAL growth factor receptor-tyrosine kinase inhibitor Effectiveness
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The relationship between tyrosine kinase inhibitor therapy and overall survival in patients with non-small cell lung cancer carrying EGFR mutations 被引量:4
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作者 Hidekazu Suzuki Tomonori Hirashima +7 位作者 Norio Okamoto Tadahiro Yamadori Motohiro Tamiya Naoko Morishita Takayuki Shiroyama Tomoyuki Otsuka Kanako Kitai Ichiro Kawase 《Chinese Journal of Cancer》 SCIE CAS CSCD 2013年第3期136-140,共5页
For patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer, the relationship between the dose or duration of treatment with tyrosine kinase inhibitor (TKI) and overall survival remains unc... For patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer, the relationship between the dose or duration of treatment with tyrosine kinase inhibitor (TKI) and overall survival remains unclear. Here, we analyzed clinical data of 39 patients who were diagnosed with EGFR mutation-positive non-small cell lung cancer and treated with TKI, but subsequently died. Several parameters were measured in this study: overall survival; first, second, and overall TKI therapy durations; first TKI intensity (actual dose/normal dose); and TKI rate (overall TKI therapy duration/overall survival). The response rate to TKI therapy was 50% , and the median survival was 553 days. After TKI therapy failed, 38.5% patients were re-challenged with TKI. We observed a moderate relationship [r = 0.534, 95% confidential interval (CI) = 0.263 to 0.727, P < 0.001] between overall TKI therapy duration and overall survival. However, we found no relationship between overall survival and first TKI intensity (r = 0.073, 95% CI = -0.380 to 0.247, P = 0.657) or TKI rate (r = 0.0345, 95% CI = -0.284 to 0.346, P = 0.835). Nonsmall cell lung cancer patients with mutation-positive tumors remained on TKI therapy for, on average, 33% of the overall survival time. These findings suggest that patients with EGFR mutation-positive tumors should not stick to using TKIs. 展开更多
关键词 酪氨酸激酶抑制剂 非小细胞肺癌 治疗剂量 肿瘤患者 EGFR 生存期 突变 表皮生长因子受体
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