EGFR突变晚期非小细胞肺癌的一线治疗进展

表皮生长因子受体(EGFR)突变在非小细胞肺癌中发生率高,酪氨酸激酶抑制剂(TKI)对EGFR突变患者有效率高、不良反应低,是EGFR突变晚期NSCLC患者的一线标准治疗。但EGFR-TKI应用一段时间后不可避免地会出现耐药。研究者在EGFR-TKI和化疗、抗血管生成治疗、放疗及免疫治疗等的联合应用领域进行了诸多尝试,显著延缓了疾病进展或耐药的发生,并转化为具有临床意义的生存获益。本文就EGFR突变晚期NSCLC患者一线治疗进展作一综述。     

基于GEO数据库的EGFR或KRAS突变型非小细胞肺癌耐药基因表达谱分析

目的 通过对相关数据库数据分析,探究NSCLC中EGFR和KRAS突变与耐药基因表达的关系,以及对患者生存和预后的影响.方法 对NCBI中GEO数据库中的数据集数据进行表达量分析、生存分析和相关性分析.结果 ①研究分析表明,ABCC1、GSTP1、MGMT1和RRM1基因在NSCLC组织中存在明显的高表达(P<0.0001;P<0.0001;P=0.0014;P<0.0001);而ERCC1和TUBB3基因表达差异没有统计学意义(P=0.3922;P=0.4583).②在KM组中,TUBB3、ABCC1和XPA基因存在明显的高表达(P=0.0169;P=0.033;P=0.0165),而在EM组中只有ABCC1存在明显的高表达(P=0.0002).③在KM组中ABCC1和XPA的表达情况呈正相关(P=0.025,γ=0.4992);而它们与TUBB3的表达情况呈负相关(P=0.0075,γ=-0.5789;P=0.0012,γ=-0.6696).④ABCC1和TUBB3的高表达会导致肺癌患者的总生存率和无复发生存率明显降低.结论 在NSCLC中EGFR或KRAS基因的突变会导致部分相关耐药基因的差异表达,这些差异表达的基因之间存在相关性,而且对患者的生存及预后又具有重要影响.     

EGFR突变型转移性非小细胞肺癌的靶向治疗疗效及安全性

目的 探讨表皮生长因子受体(EGFR)突变型转移性非小细胞肺癌的靶向治疗疗效及安全性.方法选取80例EGFR突变型转移性非小细胞肺癌患者为研究对象,根据治疗方法的不同将患者分为观察组和对照组,每组各40例.对照组采用放射治疗,观察组采用表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)吉非替尼联合放疗治疗,随访5～25个月,比较两组患者治疗4周后的疗效、治疗过程中的不良反应及随访结束时的生存情况.结果治疗4周后,观察组患者的治疗有效率和疾病控制率高于对照组(57.5％vs 35.0％,82.5％vs 62.5％),差异均有统计学意义(P﹤0.05).两组患者的不良反应均以1～2级为主,观察组患者的不良反应发生率为90.0％(36/40),与对照组的85.0％(34/40)比较,差异无统计学意义(P﹥0.05).观察组与对照组患者的中位生存时间分别为15.2个月(95％CI:12.357～18.697)和12.1个月(95％CI:9.354～15.652),差异有统计学意义(χ2=5.026,P=0.025).结论对于EGFR突变型转移性非小细胞肺癌,EGFR-TKI靶向治疗可以提高疗效,延长患者的生存时间.     

EGFR 基因状态对晚期非小细胞肺癌一线化疗的影响

目的：评价 EGFR 突变状态对晚期非小细胞肺癌（NSCLC）一线化疗近期疗效、无疾病进展时间（PFS）的影响。方法：同期非随机对照研究,依照入选标准,入组67例初治晚期 NSCLC EGFR 野生型患者及51例初治晚期 NSCLC EGFR 敏感突变型患者,分别观察客观有效率（RR）、疾病控制率（DCR）及无疾病进展时间（PFS）。结果：EGFR 野生型与 EGFR 敏感突变型的晚期 NSCLC 一线化疗的近期有效率分别为16．4％和28．6％,差异无统计学意义（P ＞0．05）,疾病控制率分别为61．2％和81．6％,差异有统计学意义（P ＜0．05）。PFS 分别为3个月与5个月,差异有统计学意义（P ＜0．05）。结论：化疗仍然是 EGFR 敏感突变型的晚期NSCLC 一线治疗的重要选择,在 DCR 及 PFS 方面,明显优于 EGFR 野生型晚期 NSCLC。     

1例EGFR突变晚期非小细胞肺癌患者靶向治疗策略探讨

患者,女,初诊年龄45岁,既往体健,否认吸烟史.2016年8月9日因咳嗽入院,行胸部CT(图1A)提示右肺上叶结节影,大小27 mm × 25 mm,分叶状,周围可见毛刺;双肺弥散分布粟粒状小结节影.2016年8月18日行活检(右上肺占位):腺癌,以腺泡状及乳头状生长方式为主;免疫组织化学:ALK-Ventana(-)...     

非小细胞肺癌EGFR靶向治疗和继发耐药机制的研究进展

非小细胞肺癌(non-small cell lung cancer,NSCLC)是最常见的肺癌亚型,表皮生长因子受体(epidermal growth factor receptor,EGFR)小分子靶向药物治疗显著地改善了晚期患者的总生存期(overall survival,OS)和生存质量,但几乎所有患者在接受治疗后均出现继发耐药。继发耐药的分子机制虽然取得了一定进展但尚未完全明确。本文结合最新文献阐述了该领域的最新研究进展,包括最新EGFR基因酪氨酸激酶(tyrosine-kinase inhibitor,TKI)域突变的研究、靶向药物的研发和临床试验结果、继发耐药的各种分子机制以及潜在克服耐药的新药物和治疗策略。对于接受EGFR小分子靶向药物治疗出现继发耐药的患者,亟需通过更加全面的分子分型检测明确耐药的分子机制,才能实现个体化治疗。      

非小细胞肺癌EGFR基因突变异质性研究进展

 表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKIs）在EGFR基因活化突变阳性晚期非小细胞肺癌（NSCLC）患者中疗效显著,然而,同样是EGFR活化突变阳性的NSCLC患者接受EGFR-TKIs治疗后,疗效仍有明显差异;同一个患者的不同瘤灶也会对EGFR-TKIs出现不同的反应,这些现象可能与EGFR基因突变异质性有关,同一瘤灶的不同部分、同一患者的不同瘤灶、以及同一瘤灶治疗前后EGFR突变状态都有可能不一致。本文将从这三个方面对EGFR突变异质性研究进展作一综述。     

表皮生长因子受体酪氨酸激酶抑制剂耐药后非小细胞肺癌治疗研究进展

表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor-tyrosine kinease inhibitors ,EGFR-TKIs）对EGFR 敏感突变非小细胞肺癌（non small cell lung cancer,NSCLC ）除了其卓越的疗效,也如其他药物一样最终不可避免地发生耐药。EGFR 基因突变是最常见的肺癌驱动基因之一,针对 EGFR-TKI 耐药后的处理,目前虽无固定治疗模式,但临床进行了大量的探索性研究及治疗对策的探讨,部分结果对临床治疗这类患者有一定启示。本文将就近年具有代表性的研究及进展做一论述。     

EGFR抑制剂治疗非小细胞肺癌新进展

EGFR是NSCLC的一个治疗靶点,临床应用EGFR抑制剂主要包括小分子酪氨酸激酶抑制剂(TKI)和单克隆抗体,2004年第40届ASCO年会报道了抗EGFR单克隆抗体和TKI在NSCLC的研究进展,现进行回顾性综述.     

浅谈晚期非小细胞肺癌EGFR-TKIs耐药后治疗

刚刚进入新世纪,肿瘤分子靶向治疗犹如浪潮席卷,冲击着我们对肿瘤的惯性思维,改变着治疗肿瘤的策略.堪称靶向治疗时代弄潮儿的表皮生长因子受体-酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitors,EGFR-TKIs)在晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)个体化治疗中独领风骚.在短短几年时间内,涉及EGFR-TKIs治疗晚期NSCLC的各类研究层见叠出,证据亦越来越多.     

Multi-targeted therapies in non-small cell lung cancer

Current treatment modalities provide limited improvement in the natural course of lung cancer, and prognosis remains poor. Lung cancer is a malignancy with great molecular heterogeneity. The complexity of the signaling process leading to cancer cell proliferation and to the neoplastic phenotype supports the necessity of interfering at different stages to avoid cancer cell resistance to therapy. For this reason, new strategies for the simultaneous inhibition of multiple molecular targets are being pursued.     

非小细胞肺癌耐药分子指标研究进展

化疗在治疗非小细胞肺癌(NSCLC)中占有重要地位，但其联合化疗的有效率也只有30％～40％，并且这个水平已达到了一个新的平台阶段。影响肺癌患者化疗疗效的主要原因是肿瘤细胞对抗癌药的抗药性，其耐药机制非常复杂，与耐药基因：MDRI、MRP、LRP，GST、拓扑异构酶Ⅱ质和量的改变、β-微管蛋白基因突变、FGF等多种因素有关。前瞻性进行分子指标的测定，是指导肺癌患者化疗用药、进行个体化治疗、提高化疗疗效的关键。     

Emerging targeted therapies in non-small cell lung cancer

Lung cancer is the leading cause of cancer-related deaths in United States, accounting for more than one-fourth of the deaths annually. Although comparatively rare and relatively less studied, genetic abnormalities other than epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangements, and Kirsten rat sarcoma (KRAS) mutations account for significant proportion of the driver mutations identified thus far. The targeted agents against B-rapidly accelerated fibrosarcoma (BRAF) V600E mutation, MNNG-HOS transforming gene (MET) pathway, ROS1 rearrangement, rearranged during transfection (RET) rearrangement, and HER2 pathways offer promising therapeutic options. Recruiting patients with these rarer mutations to well-designed, large multicenter trials to further validate the use of targeted agents remains a challenge. The clinical data and ongoing trials with these agents are reviewed in this article.     

非小细胞肺癌的分子靶向治疗

与传统细胞毒性化疗相比,分子靶向治疗能更特异性作用于肿瘤而毒性反应较轻。新的靶向治疗药物得到发展,并相继在晚期非小细胞肺癌一线、二线治疗中进行临床试验,其中有的药物显示了较好的疗效。本文对近年来关于非小细胞肺癌靶向治疗的临床试验进行回顾。     

Targeted therapies in the treatment of non-small cell lung cancer

New targeted treatments offer an important opening towards the improvement of the results in the treatment of lung cancer. Currently two types of therapeutic targets are developed successfully in the treatment of advanced non-small cell lung cancer: tumour angiogenesis and growth factor receptors. Therapeutic drugs are small molecules inhibitors and the monoclonal antibodies. Bevacizumab is a monoclonal antibody against vascular endothelial growth factor receptor, VEGF, an important molecule in tumour angiogenesis. The combination of bevacizumab with first line chemotherapy increases the median survival of advanced NSCLC with a few weeks. At this moment no biomarker predicting efficacy that can help in the selection of patients is unfortunately available for this expensive treatment, although it is important to select patients based on specific contra-indications. The epidermal growth factor receptor (EGFR or HER1) is activated in NSCLC by several mechanisms. The small molecules erlotinib and gefitinib are targeting the intracellular kinase domain of the EGF receptor, thus inhibiting the signal transduction cascade. Erlotinib is currently registered and reimbursed in Belgium. The concomitant use of these small molecules with chemotherapy is ineffective in non-selected NSCLC patients. On the other hand, these molecules have great activity in patients with tumours having a constitutionally activated EGFR. Changes in the kinase domain of the receptor give rise to extremely high response rates and unexpectedly improved survival duration in patients with NSCLC. Currently studies are exploring whether erlotinib should be employed in the first line treatment of NSCLC. The FIELT study is a translational academic and multicentre phase II study in Belgium and Luxemburg addressing this issue. Specific mechanisms of resistance for these agents are gradually discovered and the new drugs being able to overcome these resistances are at the horizon.     

Topoisomerase IIalpha and other drug resistance markers in advanced non-small cell lung cancer

Resistance to chemotherapy is common in non-small cell lung cancer. The aim of this study was to investigate the prognostic impact of in vitro established drug resistance markers on the response to chemotherapy in patients with advanced non-small cell lung cancer. Samples of 38 patients were analyzed by immunohistochemical staining, for topoisomerase IIalpha and IIbeta, Ki-67, MRP and LRP. In addition, mutation analysis of the topoisomerase IIalpha gene, the B/DNBS and the Tyr804 region, was performed. Lung tumor biopsies were taken prior for treatment with one of the following regimens; cisplatin/paclitaxel, cisplatin/VM26 or VP16, or carboplatin/VP16/ifosfamide. Seventeen patients obtained a partial response, 12 had stable disease and nine patients had progressive disease. None of the investigated markers was related with overall response rate. In one sample a point mutation in the B/DNBS region of the topo IIalpha gene was detected which substitutes IIe(510) with Val. This tumor had a partial response to four courses of cisplatin/VP16 treatment. The survival analysis showed that the patients with high topo IIalpha expressing tumors had a significantly worse survival compared with the patients with low or intermediate topo IIalpha expressing tumors. In conclusion, no relation was observed between expression of topoisomerase IIalpha, IIbeta, Ki-67, MRP or LRP and response rate. Furthermore, worse survival was seen in patients with high topoisomerase IIalpha expressing tumors. In one tumor sample, a newly described mutation in the B/DNBS region of the topo IIalpha gene was detected, which does not appear to be related to drug resistance.