肺癌靶向药物治疗新靶点和耐药特点

摘 要：近年来肺癌的靶向治疗取得了很大的进展,多种分子驱动基因陆续被发现,如MET、Her-2、RET、KRAS、BRAF、NTRK、MEK、TROP2过表达、FGFR通路异常等。针对新靶点设计的药物层出不穷。但是患者在接受靶向治疗一段时间后往往会不可避免地出现靶向药耐药的问题。全文对肺癌靶向药物治疗中的新靶点和耐药特点作一综述。     

肺癌靶向治疗的新境界:活得更长,活得更好

分子靶向治疗是21世纪肺癌治疗最具希望的治疗策略,与传统的细胞毒药物不同,分子靶向治疗可以特异性地作用于肿瘤细胞的某些特定位点,高度选择性的杀死肿瘤细胞而不杀伤或仅很少损伤正常细胞,靶向治疗药物最大的特点是安全性和耐受性极好,毒副作用轻微,临床应用具有非常大的优势。近年来靶向治疗以惊人的速度和独特的疗效引起了广大从事肿瘤治疗的广泛关注,新的靶向治疗药物Et新月异,新的治疗方案、治疗策略层出不穷,本文对近来有关晚期肺癌靶向治疗的最新研究作一综述,希望对肺癌临床研究工作者有所帮助。     

晚期非小细胞肺癌ALK融合基因及其他少见驱动基因阳性靶向治疗进展

靶向治疗是驱动基因阳性的晚期非小细胞肺癌重要的治疗手段之一,这个领域的治疗进展日新月异,包括新靶点的发现,新药物的问世以及靶向联合治疗方案的应用等,同时研究人员也深入地研究了各种靶向药物原发或获得性耐药机制。本综述旨在总结间变淋巴瘤激酶融合基因（anaplastic lymphoma kinase, ALK）及其他少见驱动基因阳性的非小细胞肺癌靶向治疗的新进展。     

肺癌靶向治疗研究:以文献计量学和可视化分析描述的热点与趋势

目的:通过文献计量学分析方法,阐述并分析肺癌靶向治疗的研究热点与趋势。方法:文章检索了万方数据库、Web of Science、SooPAT(中国专利)数据库近10年来国内外肺癌靶向治疗的相关文献,以文献计量学方法,分析并归类了肺癌靶向治疗的研究热点与时效变迁的趋势。结果:在万方数据库3 744篇肺癌靶向治疗的中文文章中,发现作用于表皮生长因子受体基因突变位点的分子靶向药物-吉非替尼治疗非小细胞肺癌的研究是中国学者近10年的主要研究热点;在近10年Web of Science数据库中检索到的810篇英文文章及参考文献显示,西妥昔单抗、贝伐单抗、纳武单抗、吉非替尼、厄洛替尼和环唑替尼为这10年肺癌治疗领域靶向治疗的热点药物,而多种靶向药物的联合治疗、晚期非小细胞肺癌的靶向治疗效果和肺癌靶向治疗后的脑转移也成为近5年该领域的国际关注热点;中国肺癌靶向治疗领域的254项有权专利的分析显示,申报了专利的主要药物包括酸敏感的吉非替尼-氟硼二吡咯衍生物、顺铂抗肺癌主动靶向隐形类脂质体等。结论:文章采用文献计量学的量化分析技术,呈现出近10年肺癌靶向治疗已成为该领域专业研究者持续关注的热点,而如何选择正确的靶向药物或药物组合方案来解决肺癌治疗中的耐药性问题,同时最大程度地减少患者的不良反应,以延长患者的生存率,应是未来集中研究的方向。     

非小细胞肺癌的分子靶向治疗进展

目前在全球范围内肺癌已成为发病率和死亡率增长最快、严重危害人类健康和生命的恶性肿瘤之一.在我国肺癌病死率已居肿瘤死亡率首位,其中非小细胞肺癌(NSCLC)约占肺癌的80%以上,且多数患者确诊时已属晚期,因此内科治疗仍是肺癌的主要治疗方法.但近十年来以化疗为主的治疗手段并未使非小细胞肺癌的疗效获得突破性进展.20世纪90年代以来,关于肺癌的分子靶向治疗研究不断深入,其中以表皮生长因子受体和肿瘤血管生成作为靶点的药物为主,部分药物已经在晚期NSCLC治疗中显示出较好的临床疗效.21世纪分子靶向治疗已取得了飞跃的进展,许多新的靶向性治疗研究为NSCLC治疗提供新的治疗途径.本研究将从以表皮生长因子受体为靶点药物,抗肿瘤血管生成药物以及多靶点抗肿瘤药物3个方面就目前非小细胞肺癌靶向治疗的研究进展作一介绍.     

非小细胞肺癌术前新辅助靶向治疗2例

自2005年2月靶向药物吉非替尼（易瑞沙）上市以来,靶向治疗广泛应用于晚期非小细胞肺癌二线或三线治疗,但术前新辅助靶向治疗尚是一种新的尝试,鲜见报道。2007年4月至2008年5月,浙江医院收治2例新辅助靶向治疗肺癌病人,报告如下。     

非小细胞肺癌新辅助靶向及免疫治疗研究进展和展望

肺癌是全球发病率和死亡率最高的恶性肿瘤。近年来,随着新型药物的出现和治疗模式的优化,肺癌患者的预后已有一定改善。新辅助治疗是指对潜在可接受手术切除的患者,先给予术前抗肿瘤治疗后再行手术治疗。新辅助治疗通过术前治疗可以缩小肿瘤体积,降低肿瘤分期;并且可以杀灭患者机体中循环肿瘤细胞及微转移病灶,令患者远期生存获益。靶向治疗及免疫治疗已被应用于晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的一线治疗。因此,有临床试验尝试将以上两种治疗手段应用于早期可切除NSCLC患者的新辅助治疗。本文针对新辅助靶向及免疫治疗对早期可切除NSCLC患者的疗效、治疗中的潜在风险予以综述,并探讨新辅助治疗的未来发展方向。     

放疗联合分子靶向药物治疗非小细胞肺癌的研究进展

目的 随着对肿瘤和正常组织放射生物学机制的深入研究以及分子靶向药物对放射生物学机制影响的进一步认识,出现了许多联合放疗和分子靶向药物的临床前期和临床试验,初步验证了这种联合治疗模式的可行性和疗效。本文就放疗联合分子靶向药物治疗非小细胞肺癌的可能机制和临床试验的初步结果作一综述。     

肺癌精准治疗的发展与展望

目前,肺癌仍然是我国发病率和死亡率较高的恶性肿瘤。传统放化疗疗效有限,肺癌治疗新药物和新方案的探索一直在进行中。过去20多年,随着分子靶向和免疫治疗的飞速发展,临床疗效不断刷新,越来越多的癌症患者从中获益。肺癌治疗方法日新月异,是实体肿瘤精准治疗领域的“排头兵”。本文梳理了肺癌精准靶向和免疫治疗的发展历程,并对存在的问题及未来发展方向进行探讨。     

中医药维持治疗晚期非小细胞肺癌的可行性探讨

晚期非小细胞肺癌维持治疗越来越受肯定,现以化疗或靶向治疗模式为主,但化疗药物的毒性蓄积,甚至过度治疗等问题却成为维持化疗的瓶颈,靶向药物的价格昂贵也给患者维持带来不便,中医药治疗晚期肺癌在改善临床症状、提高生活质量及延长生存期方面彰显优势.全文就中医药维持治疗晚期肺癌的可行性作一分析.     

Current management of advanced non-small cell lung cancer: targeted therapy

Lung cancer is one of the most frequent causes of cancer-related death in the United States. For patients with advanced non-small cell lung cancer (NSCLC), chemotherapy, alone or in combination with radiation therapy, is considered the standard treatment. Although this treatment may result in a modest improvement in patient survival, overall prognosis of these patients remains dismal, and the treatment is nonspecific, nonselective, and toxic. Therefore, new therapeutic strategies are needed. During the past decade, several molecules that contribute to lung cancer progression and metastasis have been identified. Growth factors and proangiogenic factors have been the focus of intense research in cancer since therapeutic approaches for their inhibition do exist. The role of these factors was studied in different organs and tumors and was found to be phenotypically distinct. Several molecular targeted therapies have shown efficacy and had been approved for treatment of specific cancers. Most advanced in clinical research for lung cancer are targeted therapies that inhibit the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF) signaling pathways. Others are signaling pathway inhibitors. The first targeted therapy for lung cancer is gefitinib, an EGFR inhibitor, which was approved in several countries in 2003. Goals of molecular targeted therapy studies include the following: better understanding of the exact role of particular growth factors in specific tumors; establishment of new clinical study designs for biological agents; and tailoring appropriate combinations of conventional chemotherapy and/or radiotherapy with biological therapy for specific patients. Achievement of these goals will hopefully lead to incorporation of biological therapy into the current anticancer arsenal, for the benefit of lung cancer patients.     

肺癌驱动基因及其靶向治疗药物

随着肿瘤分子生物学的发展,针对肺癌驱动基因的分子靶向治疗已成为晚期肺癌不可或缺的一部分。目前最成功的例子就是针对表皮生长因子受体（EGFR）和间变性淋巴瘤激酶（ALK）的靶向治疗。现在越来越多的肺癌驱动基因突变已被发现,包括ROS1基因融合、成纤维细胞生长因子1扩增、KRAS、BRAF和PIK3 CA基因突变等。明确这些基因突变的频率及临床意义,对指导肺癌的临床治疗有着重要的意义。     

Recent advances in lung cancer: summary of presentations from the 47 th annual meeting of the American Society of Clinical Oncology (ASCO) 2011

In the last several years, we have made slow but steady progress in developing new treatment strategies for patients with lung cancer. The use of molecularly targeted therapy has made a significant impact on the outcomes of patients with lung cancer. Further research is ongoing to identify more effective ways to target lung cancer. In the recently concluded 47 th annual meeting of the American Society of Clinical Oncology, there were several presentations on novel targeted therapies for lung cancer, in addition to the effective and optimal use of existing cytotoxic and targeted therapies for lung cancer. For this review, we have selected presentations that primarily have an impact on clinical practice, and some presentations regarding emerging therapeutic agents.     

非小细胞肺癌脑转移治疗的研究进展

肺癌是全球范围内发病率和死亡率最高的恶性肿瘤,非小细胞肺癌（non-small cell lung cancer,NSCLC）约占肺癌的80%,其中超过40%的晚期NSCLC患者在疾病病程中会发生脑转移,导致预后不良。传统的治疗方法如单纯放疗,化疗,外科手术对于改善肺癌脑转移的预后非常有限。近些年来随着立体定向放射治疗、靶向治疗的发展,尤其是化疗联合靶向,放疗联合靶向等交叉领域的联合治疗,NSCLC脑转移患者的生存质量得到提高,中位总生存期（median overall survival,mOS）得以延长。然而对于NSCLC脑转移的最佳治疗方案,仍然存在争议,本文将针对NSCLC脑转移领域的最新研究进展进行阐述,以期对肺癌脑转移患者选择合理治疗方案提供理论依据。      

胰岛素样生长因子结合蛋白-2与肺癌关系的研究进展

胰岛素样生长因子结合蛋白-2（Insulin like growth factor binding protein -2,IGFBP-2）作为肺癌高敏感的生物标记物,在肺癌的发生、发展及治疗中扮演重要的角色。研究显示其通过激活IGF1R及整合素介导的信号转导通路促进肿瘤的进展;且目前发现其在肺癌的靶向治疗中也起着重要的作用,有望成为肺癌治疗的新靶点,因此本文就IGFBP-2与肺癌的关系进行总结及综述。     

局部晚期NSCLC放疗联合分子靶向治疗的研究进展

对于不能手术切除的局部晚期NSCLC,单纯放疗或放化疗是主要治疗手段,但总体疗效并不理想。近些年来,分子靶向治疗使局部晚期肺癌的治疗有了突破性进展,其中EGFR抑制剂和VEGF抑制剂的应用较为广泛。目前,对于局部晚期NSCLC越来越多的研究侧重于放疗联合分子靶向治疗方面,现有的Ⅰ-Ⅲ期临床研究显示,放疗联合分子靶向这种新治疗模式能否与同步放化疗、序贯放化疗和单纯放疗这三种目前现有的治疗模式相比,有待进一步探究。本文针对局部晚期的NSCLC放疗联合靶向治疗进行系统性的分析。     

Future trends in patient-reported outcomes assessment for patients with advanced-stage lung cancer receiving targeted therapy

Recent advances in cancer cell biology have led to the development of therapeutic agents that target pathways critical to the development and progression of disease. These so-called "targeted therapies" might offer patients a more tolerable alternative to traditional systemic chemotherapy that often achieves therapeutic benefit at the cost of debilitating side effects. Several targeted agents have been recently tested in clinical trials of advanced-stage lung cancer. As interest in these therapies grows, an understanding of their impact on the patient's well-being will be important. Patient-reported outcome measures such as formal assessments of health-related quality of life and disease symptoms provide a useful means for addressing the impact of therapy from the perspective of the patient. We summarize the most commonly used measures of health-related quality of life in clinical trials of advanced-stage lung cancer. Although existing measurement systems do provide adequate coverage of many important patient-related outcome issues, the advent of targeted therapies in advanced-stage lung cancer does expose several measurement gaps. We highlight some of these gaps by reviewing a representative sample of recently conducted clinical trials of targeted lung cancer therapy and offer insight as to how these gaps can be filled. We also briefly discuss a set of issues unique to patients receiving targeted therapy (eg, perceptions of treatment efficacy, treatment compliance, patient satisfaction, and treatment convenience) and consider a few methodologic concerns unique to patients with advanced cancer.