表皮生长因子在肺癌治疗中的应用

表皮生长因子(EGF)及受体信号通路在非小细胞肺癌(NSCLC)的发生和发展中起重要作用.本文综述肺癌EGF及其受体(EGFR)的一般特性、作用机制、生物学功能、酪氨酸激酶拮抗剂(TKI)在肺癌靶向治疗中的作用以及EGF肿瘤疫苗治疗NSCLC的价值.     

Wnt/β-catenin信号通路在非小细胞肺癌中作用的研究进展

Wnt/β-catenin信号通路在胚胎发育和细胞增殖、分化等生理过程中扮演着重要角色,同时它在非小细胞肺癌(non-small cell lung cancer, NSCLC)的肿瘤干细胞(cancerstemcell, CSCs)的维持、血管生成和上皮间充质转化(epithelial-mesenchymaltransition, EMT)中起着至关重要的作用。有多项研究证实Wnt/β-catenin信号通路在NSCLC中被显著激活,随着对Wnt/β-catenin信号通路的研究,靶向Wnt/β-catenin信号通路疗法在NSCLC的治疗中取得了显著成效。本文对Wnt/β-catenin信号通路在NSCLC发生和发展中的作用以及治疗研究进行概述。     

非小细胞性肺癌个体化治疗的研究进展

<正>肺癌是全球发病率和病死率最高的肿瘤,其中约80%为非小细胞肺癌(non-small cell lung cancer,NSCLC)。化疗在NSCLC的临床治疗中占有重要地位,但化疗的有效率低、毒副作用大,使得总体疗效并不乐观[1]。近年来,随着基因组学和蛋白质组学的发展,个体化治疗时代已经到来。我们综合分析了与化疗耐药相关的基因及表达情况,为不同类型的NSCLC患者个体化治疗提供参考。一、切除修复交叉互补基因1(ERCC1)ERCC1是核苷酸切除修复系统家族中的标志基因,是一种DNA修复基因,在肺癌细胞的修复过程中对DNA损伤识     

BIM在晚期非小细胞肺癌治疗中的作用

肺癌是全世界范围内发病率和死亡率最高的恶性肿瘤,其中非小细胞肺癌（non-small cell lung cancer,NSCLC）是肺癌中最常见的类型。随着对肺癌发病机制、生物学行为的深入研究及基因检测水平的提高,以表皮生长因子受体（epidermal growth fac? tor receptor,EGFR）和间变淋巴瘤激酶（anaplastic lymphoma kinase,ALK）为靶点药物的发现,在晚期NSCLC个体化治疗的发展中具有里程碑式的意义。BIM（Bcl-2 interaction mediator of cell death）是Bcl-2家族促凋亡蛋白中的一员,参与细胞凋亡的重要介质。近年来,有研究证实BIM的表达水平及多态性会影响晚期NSCLC靶向治疗及化疗的疗效。本文就BIM及其在晚期NSCLC靶向治疗及化疗中的作用进行综述。      

PI3K/Akt/mTOR信号转导通路与非小细胞肺癌

肺癌是目前世界上发病率和死亡率最高的恶性肿瘤之一,其中非小细胞肺癌(non-small cell lung cancer,NSCLC)占肺癌的75%-85%,确诊时多属中晚期,常规放、化疗效果欠佳,5年生存率仅为5%-10%.PI3K/Akt/mTOR信号通路作为细胞内重要信号转导通路之一,通过影响下游多种效应分子的活化状态,与NSCLC的发生发展密切相关.本文综述了PI3K/Akt/mTOR信号通路的组成,其抑制凋亡、促进增殖的关键作用以及在NSCLC中的研究现状,以期为NSCLC的治疗寻找潜在的靶点.     

易瑞沙治疗晚期非小细胞肺癌临床观察

受体酪氨酸激酶(receptor tyrosine kinases,RTK)中的erbB家族包括4个成员,表皮生长因子受体(epidermal growth factor re-ceptor,EGFR)是其成员之一,在非小细胞肺癌(non-small cell lungcancer,NSCLC)中,EGFR-RTK占40%~80%,对肿瘤的生长、转移、血管生成及对放化疗的抗拒起着重要作用,其过度表达常与预后不良相关[1]。易瑞沙(IRESSA,阿斯利康公司)是与ATP竞争性结合的小分子,能选择性抑制EGFR-RTK,影响信号传导。我们用易瑞沙治疗化疗失败的NSCLC患者51例,结果报道如下。1临床资料1.1一般资料病例选择标准:经组织细胞学确…     

非小细胞肺癌PI3K/AKT/MTOR信号通路的研究现状与进展

PI3K/AKT/MTOR通路是人体的重要信号通路,是通过逐级磷酸化下游蛋白,控制肿瘤发生发展中至关重要的细胞生物学过程,包括细胞的增殖、凋亡,细胞周期的调节及血管形成等.肺癌是发病率和病死率增长最快的恶性肿瘤,其中非小细胞肺癌(NSCLC)是其主要类型.研究发现PI3K/AKT/MTOR通路的失调对NSCLC的发生发展有重要的作用.近年来,免疫治疗的发展为NSCLC提供了一个新的治疗方向.免疫治疗可联合其他治疗方法,包括放疗、化疗和靶向治疗等,在NSCLC的综合治疗中起到协同作用,从而提高NSCLC治疗的效果.最近的研究表明PI3K/AKT/MTOR通路通过影响微环境内免疫细胞的活性及PD-L1的表达对肿瘤免疫微环境产生影响,参与免疫抑制微环境的形成,促进肿瘤发生发展.因此,PI3K/AKT/MTOR通路阻断药与免疫治疗联合的治疗方式成为NSCLC治疗的研究热点.本文旨在对PI3K/AKT/MTOR通路在NSCLC中的研究现状及进展进行综述.     

非小细胞肺癌的生物治疗研究进展

肺癌是恶性肿瘤相关死亡的首要原因之一,发病率在多数国家仍在上升,特别是发达和发展中国家.肺癌分为非小细胞肺癌(NSCLC)和小细胞肺癌(SCLC)两大类.其中,NSCLC约占肺癌总发生率的85％;大部分患者发现时已属于晚期,常规治疗有一定局限性,疗效不理想.近年来,生物治疗包括靶向治疗、树突状细胞、肿瘤疫苗(DC肿瘤疫苗)等在NSCLC临床研究与应用中取得可喜进展,本文就近年来NSCLC的生物治疗方面作一综述.     

液体活检在非小细胞肺癌靶向治疗中应用

目的液体活检技术在肿瘤的检测方法中是尤为重要的检测手段。其在指导非小细胞肺癌(non-small cell lung cancer,NSCLC)靶向药物的选择、耐药监测以及预后评估等方面具有重要作用,本研究分析近年来国内外液体活检在NSCLC靶向治疗中的应用,以期明确液体活检对NSCLC靶向治疗的指导作用,进而有助于指导靶向药物在NSCLC治疗中的应用。方法应用PubMed、中国知网及中国期刊全文数据库检索系统,以"液体活检、循环肿瘤DNA、循环肿瘤细胞、靶向治疗、非小细胞肺癌"为关键词,检索2009-2019年发表的相关文献。纳入标准:(1)液体活检的机制;(2)靶向治疗在NSCLC中的应用;(3)NSCLC的治疗。排除标准:(1)中文非核心期刊的文献和英文非SCI收录文献;(2)结果重复且相对陈旧的实验研究。根据纳入标准和排除标准,最终29篇文献纳入分析。结果液体活检技术可对NSCLC的诊断、治疗及预后评估进行实时动态监测,及时获取肿瘤基因突变信息,在指导靶向药物选择,对耐药监测以及预后评估等方面具有重要作用。结论液体活检对指导NSCLC患者的靶向治疗具有重要作用,有助于NSCLC患者靶向药物治疗的选择。     

CTP和MVP方案治疗非小细胞肺癌62例临床观察

目前肺癌在全球范围严重威胁人类健康,非小细胞肺癌(NSCLC)占所有肺癌死亡的80%,约3/4的NSCLC患者诊断时已是Ⅲ期或Ⅳ期,已经失去了手术切除的机会,化疗是治疗中晚期NSCLC的重要手段.     

雌激素与非小细胞肺癌的相关研究进展

肺癌死亡率位居全球恶性肿瘤之首,其中约85%为非小细胞肺癌（non - small cell lung cancer, NSCLC）。虽然其治疗手段有新的进展,但死亡率仍然居高不下。越来越多的证据表明,雌激素及雌激素受体参与了 NSCLC 的发生和发展。雌激素的治疗已成为目前 NSCLC 诊治的一大热点,本文将雌激素及抗雌激素治疗在 NSCLC 中的作用做一综述。     

Emerging antiangiogenic therapies for non-small-cell lung cancer

Lung cancer remains the leading cause of cancer-related deaths. Antiangiogenic therapy has increasingly been studied for advanced non-small-cell lung cancer (NSCLC). Bevacizumab is the only approved antiangiogenic agent for NSCLC and has shown progression-free survival benefits in large Phase III studies and an overall survival benefit in the Phase III E4599 trial in advanced nonsquamous NSCLC. New antiangiogenic treatment strategies are being evaluated that target multiple receptors within a family (VEGF receptor [VEGFR]-1, VEGFR-2) or multiple angiogenic pathways (targets VEGFR and PDGF receptor pathways), and agents that inhibit alternative mediators of angiogenesis (integrins and established vasculature). As data become available from ongoing studies, it will be important to determine how these new antiangiogenic agents will best fit into the current NSCLC treatment paradigm.     

Emerging antiangiogenic therapies for non-small-cell lung cancer

Lung cancer remains the leading cause of cancer-related deaths. Antiangiogenic therapy has increasingly been studied for advanced non-small-cell lung cancer (NSCLC). Bevacizumab is the only approved antiangiogenic agent for NSCLC and has shown progression-free survival benefits in large Phase III studies and an overall survival benefit in the Phase III E4599 trial in advanced nonsquamous NSCLC. New antiangiogenic treatment strategies are being evaluated that target multiple receptors within a family (VEGF receptor [VEGFR]-1, VEGFR-2) or multiple angiogenic pathways (targets VEGFR and PDGF receptor pathways), and agents that inhibit alternative mediators of angiogenesis (integrins and established vasculature). As data become available from ongoing studies, it will be important to determine how these new antiangiogenic agents will best fit into the current NSCLC treatment paradigm.     

Fibroblast growth factor signaling in non-small-cell lung cancer

Despite recent progress in the treatment on non-small cell lung cancer (NSCLC), outcomes remain suboptimal. Treatment advances that target the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) signaling pathways highlight the need to understand the multiple convergent growth factor signaling pathways involved in the pathogenesis of NSCLC. Signaling through fibroblast growth factors (FGF), long recognized for its pro-angiogenic activity, has recently emerged as a contributing factor in the pathogenesis and progression of NSCLC through an autocrine signaling loop. In addition, this pathway may function as a mechanism of resistance to anti-EGFR and anti-VEGF treatment. Clinical experience with FGF receptor (FGFR) inhibitors is mounting, and more specific inhibitors of this signaling pathway are in development. This review describes the structure of the FGF signaling pathway, delineates its dual roles in angiogenesis and proliferation in NSCLC, evaluates FGF ligand and receptor expression as prognostic biomarkers in NSCLC, and discusses the development of FGF pathway inhibitors for the treatment of lung malignancies.     

The potential for crizotinib in non-small cell lung cancer: a perspective review

Tyrosine kinases have a crucial role as key regulators of signaling pathways that influence cell differentiation and growth. Dysregulation of tyrosine kinase-mediated signaling is understood to be an important oncogenic driver. Genetic rearrangements involving the tyrosine kinase anaplastic lymphoma kinase (ALK) gene occur in non-small cell lung cancer (NSCLC), anaplastic large cell lymphomoas, inflammatory myofibroblastic tumors, and other cancers. Cells with abnormal ALK signaling are sensitive to ALK inhibitors such as crizotinib. This review will highlight the discovery of the fusion between echinoderm microtubule-associated protein-like 4 (EML4) and ALK as an oncogenic driver, recognition of other ALK gene rearrangements in NSCLC, and the confirmation that crizotinib is an effective treatment for patients with ALK-positive NSCLC. Work is underway to further define the role for crizotinib in the treatment of ALK-positive lung cancer and other cancers and to investigate the molecular mechanisms for resistance to ALK inhibition with crizotinib.     

Transcriptional Regulation of IRS5/DOK4 Expression in Non–Small-Cell Lung Cancer Cells

The insulin-receptor substrate family plays important roles in cellular growth, signaling, and survival. Two new members of this family have recently been isolated: IRS5/Dok4 and IRS6/Dok5. This study examines the expression of IRS5/DOK4 in a panel of lung cancer cell lines and tumor specimens. The results demonstrate that expression of IRS5/DOK4 is frequently altered with both elevated and decreased expression in non–small-cell lung cancer (NSCLC) tumor specimens. The altered expression of IRS5/DOK4 observed in tumor samples is not due to aberrant methylation. In vitro cell culture studies demonstrate that treatment of NSCLC cell lines with the histone deacetylase inhibitor trichostatin A (TSA) upregulates IRS5/DOK4. This finding indicates that expression is regulated epigenetically at the level of chromatin remodeling. Chromatin immunoprecipitation experiments confirm that the IRS5/DOK4 promoter has enhanced histone hyperacetylation following treatments with TSA. Finally, hypoxia was demonstrated to downregulate IRS5/DOK4 expression. This expression was restored by TSA. The clinical relevance of altered IRS5/DOK4 expression in NSCLC requires further evaluation.     

Aberrant epidermal growth factor receptor signaling and enhanced sensitivity to EGFR inhibitors in lung cancer

Epidermal growth factor receptor (EGFR) is occasionally amplified and/or mutated in non-small cell lung cancer (NSCLC) and can be coexpressed with other members of the HER receptor family to form functional heterodimers. We therefore investigated lung cancer cell lines for alterations in EGFR gene copy number, enhanced expression of EGFR and other HER family members, and EGFR coding sequence mutations and correlated these findings with response to treatment with the EGFR inhibitors and the kinetics of ligand-induced signaling. We show here that somatic deletions in the tyrosine kinase domain of EGFR were associated with increased EGFR gene copy number in NSCLC. Treatment with the specific EGFR tyrosine kinase inhibitors (TKI) gefitinib or erlotinib or the EGFR inhibitory antibody cetuximab induced apoptosis of HCC827, a NSCLC cell line with EGFR gene amplification and an exon 19 deletion. H1819, a NSCLC cell line that expresses high levels of EGFR, ErbB2, and ErbB3 but has wild-type EGFR, showed intermediate sensitivity to TKIs. In both cell lines, ligand-induced receptor tyrosine phosphorylation was delayed and prolonged and AKT was constitutively phosphorylated (but remained inhibitable by EGFR TKI). Thus, in addition to EGFR mutations, other factors in NSCLC cells, such as high expression of ErbB family members, may constitutively activate AKT and sensitize cells to EGFR inhibitors.     

Targeting epidermal growth factor receptor in lung cancer: Perspective from the Asia–Pacific region

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase of the ErbB family that is frequently overexpressed in non‐small cell lung cancer (NSCLC), and has been identified as a novel therapeutic target for lung cancer. The development of small molecule EGFR‐tyrosine kinase inhibitors (TKI) such as gefitinib and erlotinib has resulted in paradigm shift in the treatment of advanced NSCLC. The impact of EGFR‐TKI in the treatment of NSCLC is even greater in Asia–Pacific region because one of the greatest clinical benefits of EGFR‐TKI has been seen in patients of East Asian ethnicity. The discovery of somatic mutations in EGFR‐tyrosine kinase domain has so far answered some, but not all, of the questions regarding the clinical response to EGFR‐TKI in NSCLC. In addition, other molecular profiles such as KRAS mutations have also been found to play an important role in EGFR targeted therapy. In this article, we review EGFR targeted therapy in NSCLC with the focus on perspective from the Asia–Pacific region.     

ZD1839 (Iressa) in non-small-cell lung cancer

The epidermal growth factor receptor (EGFR) signaling pathway plays an important role in a number of processes that are key to tumor progression, including cell proliferation, angiogenesis, metastatic spread, and inhibition of apoptosis. EGFR is expressed or overexpressed in non-small-cell lung cancer (NSCLC), and EGFR-mediated growth has been associated with advanced disease and poor prognosis in NSCLC patients. ZD1839 (Iressa) is an orally active, selective EGFR-tyrosine kinase inhibitor that blocks EGFR signal transduction. In preclinical studies using NSCLC cell lines, ZD1839 has been shown to inhibit tumor cell growth. In addition, ZD1839, as monotherapy and in combination with commonly used cytotoxic agents, has produced growth delay in NSCLC human xenografts. Preliminary results from phase I trials in patients with advanced disease have shown that ZD1839 has excellent bioavailability, an acceptable tolerability profile, and promising clinical activity in patients with a variety of tumor types, particularly in NSCLC. ZD1839 is currently in phase III clinical development for the treatment of advanced NSCLC.