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Non-small cell lung carcinoma(nsclc):Implications on molecular pathology and advances in early diagnostics and therapeutics

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Genes & Diseases 2023年第3期10卷 960-989页

作者： Hafiza Padinharayil Jinsu Varghese Mithun Chacko John Golgodu Krishnamurthy Rajanikant Cornelia M.Wilson Minnatallah Al-Yozbaki Kaviyarasi Renu Saikat Dewanjee Rupa Sanyal Abhijit Dey Anirban Goutam Mukherjee Uddesh Ramesh Wanjari Abilash Valsala Gopalakrishnan Alex George Jubilee Centre for Medical Research Jubilee Mission Medical College and Research InstituteThrissurKerala 680005India PG&Research Department of Zoology St.Thomas CollegeKozhencheryPathanamthittaKerala 689641India Department of Medical Oncology Jubilee Mission Medical College and Research InstituteThrissurKerala 680005India School of Biotechnology National Institute of TechnologyCalicutKerala 673601India Canterbury Christ Church University Natural Applied SciencesLife Sciences Industry Liaison LabDiscovery ParkSandwich CT139FFUnited Kingdom Centre of Molecular Medicine and Diagnostics(COMManD) Department of BiochemistrySaveetha Dental College&HospitalsSaveetha Institute of Medical and Technical SciencesSaveetha UniversityChennaiTamil Nadu 600077India Department of Pharmaceutical Technology Jadavpur UniversityKolkataWest Bengal 700032India Department of Botany Bhairab Ganguly CollegeFeeder RoadBelghoriaKolkataWest Bengal 700056India Department of Life Sciences Presidency UniversityKolkataWest Bengal 700073India Department of Biomedical Sciences School of Bio-Sciences and TechnologyVellore Institute of Technology(VIT)VelloreTamil Nadu 632014India

Continuous revision of the histologic and stage-wise classification of lung cancer by the World Health Organization (WHO) provides the foundation for therapeutic advances by promoting molecular targeted and immunotherapies and ensuring accurate diagnosis. Cancer epidemiologic data provide helpful information for cancer prevention, diagnosis, and management, supporting health-care interventions. Global cancer mortality projections from 2016 to 2060 show that cancer will overtake ischemic heart diseases (IHD) as the leading cause of death (18.9 million) immediately after 2030, surpassing non-small cell lung cancer (nsclc), which accounts for 85 percent of lung cancers. The clinical stage at the diagnosis is the main prognostic factor in nsclc therapies. Advanced early diagnostic methods are essential as the initial stages of cancer show reduced mortality compared to the advanced stages. Sophisticated approaches to proper histological classification and nsclc management have improved clinical efficiency. Although immune checkpoint inhibitors (ICIs) and targeted molecular therapies have refined the therapeutic management of late-stage nsclc, the specificity and sensitivity of cancer biomarkers should be improved by focusing on prospective studies, followed by their use as therapeutic tools. The liquid biopsy candidates such as circulating tumor cells (CTCs), circulating cell-free tumor DNA (cfDNA), tumor educated platelets (TEP), and extracellular vesicles (EVs) possess cancer-derived biomolecules and aid in tracing: driver mutations leading to cancer, acquired resistance caused by various generations of therapeutic agents, refractory disease, prognosis, and surveillance.

关键词： Biomarker Clinical trial Epidemiology Histology Liquid biopsy nsclc Targeted therapy

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LncRNAs LCETRL3 and LCETRL4 at chromosome 4q12 diminish EGFR-TKIs efficiency in nsclc through stabilizing TDP43 and EIF2S1

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Signal Transduction and Targeted Therapy 2022年第2期7卷 583-594页

作者： Yankang Li Yue Shen Mengyu Xie Bowen Wang Teng Wang Jiajia Zeng Hui Hua Jinming Yu Ming Yang Cheeloo College of Medicine Shandong UniversityJinanShandong Province 250112China Shandong Provincial Key Laboratory of Radiation Oncology Cancer Research CenterShandong Cancer Hospital and InstituteJinanShandong Province 250117China Shandong University Cancer Center JinanShandong Province 250117China Department of Radiation Oncology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandong Province 250117China

Epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)are effective targeted therapy drugs for advanced nonsmall cell lung cancer(nsclc)patients carrying sensitized EGFR *** rapid development of EGFR-TKIs resistance represents a major clinical challenge for managing *** chromosome 4q12 is the first genome-wide association study(GWAS)-reported locus associated with progression-free survival(PFS)of nsclc patients treated with ***,the biological significance of the noncoding transcripts at 4q12 in nsclc remains *** the present study,we identified two 4q12 long noncoding RNAs(lncRNAs)LCETRL3 and LCETRL4 which could significantly dimmish EGFR-TKIs *** line with their oncogenic role,evidently higher LCETRL3 and LCETRL4 levels were observed in nsclc tissues as compared with normal ***,lncRNA LCETRL3 can interact with oncoprotein TDP43 and inhibit ubiquitination and degradation of ***,lncRNA LCETRL4 can bind and stabilize oncoprotein EIF2S1 through reducing ubiquitin-proteasome degradation of *** particular,elevated levels of LCETRL3 or LCETRL4 in nsclc cells resulted in stabilization of TDP43 or EIF2S1,increased levels of NOTCH1 or phosphorylated PDK1,activated AKT signaling and,thus,EGFR-TKIs *** together,our data revealed a novel model that integrates two lncRNAs transcribed from the 4q12 locus into the regulation of EGFR-TKIs resistance in *** findings shed new light on the importance of functionally annotating lncRNAs in the GWAS loci and provided insights to declare novel druggable targets,i.e.,lncRNAs,which may unlock the therapeutic potential of EGFR-TKIs resistant nsclc in the clinic.

关键词： nsclc elevated drugs

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EMP-1 Promotes Tumorigenesis of nsclc through PI3K/AKT Pathway

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2012年第6期32卷 834-838页

作者：来森艳王桂华曹小年李兆明胡俊波王晶 Cancer Research Institute Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

This study examined the role of EMP-1 in tumorigenesis of non-small cell lung carcinoma (nsclc) and the possible mechanism. Specimens were collected from 28 patients with benign lung diseases and 28 with nsclc, and immunohis to chemically detected to evaluate the correlation of EMP-1 expression to the clinical features of nsclc. Recombinant adenovirus was constructed to over-express EMP-1 and then infect PC9 cells. Cell proliferation was measured by Ki67 staining. Western blotting was performed to examine the effect of EMP-1 on the PI3K/AKT signaling. Moreover, tumor xeno-grafts were established by subcutaneous injection of PC9 cell suspension (about 5×107/mL in 100 μL of PBS) into the right hind limbs of athymic nude mice. The results showed EMP-1 was significantly up-regulated in nsclc patients as compared with those with benign lung diseases. Over-expression of EMP-1 promoted proliferation of PC9 cells, which coincided with the activation of the PI3K/AKT pathway. EMP-1 promoted the growth of xenografts of PC9 cells in athymic nude mice. It was concluded that EMP-1 expression may contribute to the development and progress of nsclc by activating PI3K/AKT pathway.

关键词： nsclc EMP-1 gene PI3K/AKT pathway tumorigenesis

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First-line anti-VEGF plus EGFR-TKI in EGFR-mutant nsclc: adding the ARTEMIS trial to the puzzle of current evidence

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Signal Transduction and Targeted Therapy 2022年第1期7卷 4-6页

作者： Susanne Hafner Institute of Pharmacology of Natural Products and Clinical Pharmacology Ulm UniversityD-89081 UlmGermany

In the ARTEMIS-CTONG1509 multicenter phase 3 study recently published in Cancer Cell,Zhou et *** the combination of the EGFR tyrosine kinase inhibitor(TKI)erlotinib and anti-angiogenic bevacizumab in treatmentnaive Chinese patients with advanced EGFR-mutant non-small cell lung cancer(nsclc).^(1) The primary endpoint of progression-free survival(PFS)was significantly exte nded from 11.2 months with erloti nib mono therapy to 17.9 mon ths with the combination.

关键词： nsclc TKI EGFR

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Erratum to DYRK1A suppression restrains Mcl-1 expression and sensitizes nsclc cells to Bcl-2 inhibitors

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Cancer Biology & Medicine 2022年第7期19卷 1109-1110页

作者： Yangling Li Dongmei Zhou Shuang Xu Mingjun Rao Zuoyan Zhang Linwen Wu Chong Zhang Nengming Lin Department of Clinical Pharmacology Hangzhou First People’s HospitalNanjing Medical UniversityHangzhou 310006China Department of Clinical Pharmacology Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang ProvinceHangzhou First People’s HospitalZhejiang University School of MedicineHangzhou 310006China Institute of Pharmacology College of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhou 311402China School of Medicine Zhejiang University City CollegeHangzhou 310015China

In the published paper1,errors appeared in Figure 1D on page *** Figure 1D,an incorrect gel image was shown for Bcl-xL in NCI-H1299 *** 1D has been updated to correct the mistake *** errors do not affect the conclusio... 详细信息

关键词： Figure nsclc restrain

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Combined targeting of CCL7 and Flt3L to promote the expansion and infiltration of cDC1s in tumors enhances T-cell activation and anti-PD-1 therapy effectiveness in nsclc

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Cellular & Molecular Immunology 2023年第7期20卷 850-853页

作者： Hong-Peng Dong Ying Li Zhen Tang Peng Wang Bo Zhong Qian Chu Dandan Lin Cancer Center Renmin Hospital of Wuhan UniversityMedical Research Institute and Frontier Science Center of Immunology and MetabolismWuhan UniversityWuhan 430071China College of Life Sciences Wuhan UniversityWuhan 430072China CAS Key Laboratory of Infection and Immunity Institute of BiophysicsChinese Academy of SciencesBeijing 10011China Taikang Center for Life and Medical Sciences Wuhan UniversityWuhan 430071China Department of Oncoogy Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

mmune checkpoint inhibitors(ICIs),represented by anti-PD-1/PD-L1 antibodies,have been widely applied in various cancers,and the efficacy of ICIs is closely associated with the tumor immune microenvironment(TIME)[1,2].We previously demonstrated that the alveolar macrophage-derived chemokine CCL7 recruited conventional type 1 dendritic cells(cDC1s)to remodel the TIME,thereby promoting the expansion of T cells to inhibit non-small cell lung cancer(nsclc)progression in KrasLSL-G12D/+Tp53fl/fl(KP)and KrasLSL-G12D/+Lkb1fl/fl(KL)mouse models[3].Here,we showed that the fusion protein PD-1Ab7,in which CCL7 was fused with the single-chain variable fragment region(scFv)of an anti-PD-1 antibody(PD-1Ab),exhibited antitumor activity superior to that of PD-1Ab in a manner dependent on *** addition,Fms-like tyrosine kinase 3 ligand(Flt3L)synergized with PD-1Ab7 to inhibit nsclc progression in both the KP and the KL mouse ***,Flt3L promoted the generation and proliferation of cDC1s,whereas PD-1Ab7 increased the infiltration and migration of cDC1s in the TIME to potentiate the activation and proliferation of T *** findings not only highlight the essential roles of the PD-1Ab-based chemokine fusion strategy in targeting cDC1s and T cells to potentiate the efficacy of ICIs for cancer prevention but also provide therapeutic lead molecules for antitumor therapy.

关键词： Flt3L nsclc prevention

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T790M mutation in stage IV EGFR-mutated nsclc patient with acquired resistance reverted to original 19Del mutation after administration of a series of precision treatments:a case report

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Precision Clinical Medicine 2018年第3期1卷 129-133页

作者： Jialong Han Ya Wang Lili Zhong Huijie Zhou Min Yu Yanying Li You Lu Yan Wang Jiang Zhu West China Hospital and West China Medical Center of Sichuan University Department of Thoracic Oncology West China HospitalSichaun University Department of IVF West China Second HospitalSichuan University

Existing studies have yet to elucidate clearly the mechanisms of secondary resistance to third generation epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs),neither is there any established standard therapy for patients resistant to third generation *** case report demonstrates a rare mutation pattern in a male patient with a pathologic diagnosis of non-small cell lung cancer(nsclc)harboring an EGFR exon 19 deletion(19Del)mutation,who then acquired an EGFR-T790M mutation after developing resistance to the first generation EGFR-TKI(gefitinib).The mutation reverted to the original EGFR-19Del mutation after the patient developed secondary resistance against the third generation TKI(osimertinib).This patient eventually achieved partial response(PR)with second generation TKI(afatinib)as a fourth-line treatment.

关键词： nsclc EGFR mutation acquired resistance driver gene

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关于《安罗替尼联合三代EGFR-TKIs治疗晚期EGFR突变阳性nsclc的疗效及影响因素分析》一文的更正

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安徽医学 2024年第9期45卷 1099-1099页

作者：《安徽医学》编辑部不详

《安徽医学》2024年第45卷第8期《安罗替尼联合三代EGFR-TKIs治疗晚期EGFR突变阳性nsclc的疗效及影响因素分析》一文中,第975、977、978和979页,作者:陈文俊、汪睿、雷宇、程怀东,因作者校对有误,药品名称“奥西替尼”出现错别字,现更正... 详细信息

《安徽医学》2024年第45卷第8期《安罗替尼联合三代EGFR-TKIs治疗晚期EGFR突变阳性nsclc的疗效及影响因素分析》一文中,第975、977、978和979页,作者:陈文俊、汪睿、雷宇、程怀东,因作者校对有误,药品名称“奥西替尼”出现错别字,现更正为:“奥希替尼”。

关键词：药品名称 EGFR突变 nsclc TKI 安徽医学疗效及影响错别字更正

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二代测序技术在nsclc中的临床应用中国专家共识(2020版)

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中国肺癌杂志 2020年第9期23卷 741-761页

作者：无周彩存王洁程颖韩宝惠卢铀王长利王哲海范云林冬梅任胜祥宋勇伍钢张艰张绪超中国临床肿瘤学会非小细胞肺癌专家委员会同济大学附属上海市肺科医院中国医学科学院肿瘤医院吉林省肿瘤医院院上海交通大学附属胸科医院四川大学华西医院天津医科大学肿瘤医院山东省肿瘤医院浙江省肿瘤医院院北京大学肿瘤医院中国人民解放军东部战区总医院华中科技大学同济医学院附属协和医院空军军医大学第一附属医院广东省人民医院

1引言肺癌是目前全球最常见、致死率最高的恶性肿瘤^([1])。2018年全球肺癌新发病例近209.4万例,占所有恶性肿瘤的11.6%,死亡病例176.1万例,占所有恶性肿瘤的18.4%^([1])。全国肿瘤登记中心数据^([2])显示,2014年我国新发肺癌患者数为7... 详细信息

1引言肺癌是目前全球最常见、致死率最高的恶性肿瘤^([1])。2018年全球肺癌新发病例近209.4万例,占所有恶性肿瘤的11.6%,死亡病例176.1万例,占所有恶性肿瘤的18.4%^([1])。全国肿瘤登记中心数据^([2])显示,2014年我国新发肺癌患者数为78.1万,死亡数达到62.6万,居所有恶性肿瘤发病和死亡人数首位。17个癌症注册中心的数据^([3])分析显示,我国肺癌患者的年龄标化5年相对生存率由2003年-200S年的16.1%仅增加至2012年-2015年的19.7%,仍不乐观。

关键词：肿瘤登记年龄标化相对生存率注册中心恶性肿瘤新发病例死亡人数 nsclc

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nsclc脑转移磁共振影像特征评价EGFR突变的研究

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第三军医大学学报 2019年第5期41卷 442-447页

作者：何容张志敏何轩肖何耿明英李松霖张玉龙王正波王阁陆军军医大学(第三军医大学)大坪医院肿瘤中心重庆400042

目的分析EGFR突变与临床非小细胞肺癌(non-small cell lung cancer,nsclc)脑转移磁共振(magnetic resonance imaging,MRI)影像特征的关系,探讨脑转移MRI特征评价EGFR突变的价值。方法收集本院2011年1月至2017年1月116例nsclc脑转移患者临床资料,应用扩增阻滞突变系统方法检测肺癌EGFR突变;回顾性分析患者MRI特征,脑转移瘤个数、大小、部位、强化方式、最大病灶瘤周水肿大小及瘤周水肿指数与EGFR突变相关性。结果 116例nsclc脑转移患者中,EGFR突变型50例(43.1%);与年龄>60岁患者相比,年龄nsclc脑转移临床特征及MRI影像可预测EGFR基因突变,为医学上无法进行EGFR突变检测的患者选用EGFR-TKI靶向治疗提供了理论依据。

关键词： nsclc 表皮生长因子受体基因突变脑转移

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