非小细胞肺癌分子靶向治疗的研究进展

肺癌作为对人类健康与生命造成威胁的一种常见恶性肿瘤,具有较高的发病率与死亡率。肺癌临床属性分为非小细胞肺癌与小细胞肺癌,其中非小细胞肺癌在全部肺癌发病中的占比高达80%~85%,且多数肺癌患者在确诊阶段已处于中晚期,加剧了临床治疗的难度。在医疗技术的不断发展下,手术、放疗、化疗、靶向治疗以及免疫治疗等方式的出现与发展为非小细胞肺癌患者的临床治疗带来新的希望,而分子靶向治疗药物的涌现,为非小细胞肺癌患者的治疗提供了新的选择。     

晚期非鳞非小细胞肺癌的药物治疗研究进展

肺癌是我国乃至全世界发病率和死亡率最高的恶性肿瘤,严重威胁人类的健康。非鳞非小细胞肺癌占其中的绝大多数,由于缺乏有效的、特异性强的早期筛查方法,许多患者被确诊时已属晚期。近年来随着多学科综合治疗的开展,其治疗效果有了很大的提高,但1年生存率仍不理想。目前针对晚期非鳞非小细胞肺癌的治疗,仍以化疗、分子靶向治疗及生物免疫治疗等综合治疗为主。本文对晚期非鳞非小细胞肺癌常用的药物治疗进展作一综述。     

延续护理在非小细胞肺癌患者出院后口服靶向药物治疗中的临床效果研究

<正>肺癌是近年来发病率增长最快、对人群健康和生命威胁最大的恶性肿瘤之一~([1])。临床上将肺癌分为小细胞肺癌和非小细胞肺癌,非小细胞肺癌主要包括腺癌、鳞癌、大细胞癌,约占全部肺癌的85%左右。大部分患者就诊时已属于晚期,失去了手术机会,化疗和放疗成了这些患者的主要治疗方法。肺癌患者一般年龄大、伴发疾病多,对全身放化疗耐受性差,治疗以姑息、支持、辅助及对症处理为主,生存质量和寿命均受到影响。最新的研究进展表明分子靶向药物给非小细胞肺癌晚期患者提供了新的治疗方向,分子靶向药物治疗比传统的化疗具有更高的选择性,毒副反应更少,患者易接受。吉非替尼作为晚期非小细胞肺癌常用的分子靶向药物,它与     

免疫靶向药物治疗非小细胞肺癌的最新研究进展

随着精准医学和生物技术的发展,除了EGFR基因,非小细胞肺癌中ALK、BRAF、HER2、KRAS、MEK1、MET、NRAS、PIK3CA、RET、ROS1等多个基因突变的研究也逐渐取得更大突破。相比化疗时代,靶向和免疫治疗显著延长了晚期非小细胞肺癌患者的生存时间,使晚期转移性肺癌患者的中位生存期延长至23～27个月,5年生存率达14.6%以上。2020年,非小细胞肺癌新药的进展和获批均呈现井喷状态,特别是靶向和免疫治疗领域产生了范式转变,每一项成功的数据都为晚期非小细胞肺癌患者的生存带来了更多的选择和希望。本文拟对2020年新上市和获批一线治疗非小细胞肺癌的免疫靶向新药进行介绍和总结,以期为临床用药提供一定的理论基础。     

非小细胞肺癌EGFR基因突变阳性的临床意义

目的：探讨非小细胞肺癌表皮生长因子受体（EGFR）第19、21号外显子突变与其临床病理特征、家族史的关系,以及对突变阳性患者使用表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）靶向治疗的效果。方法采用扩增阻滞突变系统聚合酶链反应技术对EGFR第19、21号外显子进行检测。结果162例非小细胞肺癌患者发生EGFR突变阳性63例,突变阳性率为38.89%。腺癌、女性、非吸烟者、有肺癌及其他恶性肿瘤家族史的非小细胞肺癌患者EGFR突变率明显升高,差异有统计学意义（P0.05）。非小细胞肺癌发生EGFR突变阳性使用EGFR-TKIs靶向治疗患者的中位生存期明显长于未治疗及其他药物化疗患者,差异有统计学意义（P〈0.01）。结论非小细胞肺癌患者EGFR突变筛查应作为常规临床检测指标,特别是对于有肿瘤家族史患者更具有临床意义。     

晚期非小细胞肺癌治疗的新趋势

当今肺癌研究的热点是以与肿瘤发生、发展相关的驱动基因为靶点,研发新的药物,进行有针对性的个体化分子靶向治疗,从而改善患者预后。靶向药物、新型化疗药物、抗血管新生药物以及治疗性疫苗等各种治疗手段在晚期非小细胞肺癌(NSCLC)患者的治疗中均取得了显著的进展。其中表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)对于EGFR突变阳性NSCLC患者无论在一线、维持还是二线治疗中疗效均得到肯定;替吉奥胶囊有望成为晚期NSCLC一线、二线治疗新的选择;克唑替尼是棘皮动物微管结合蛋白4与间变淋巴瘤激酶融合基因(EML4-ALK)阳性患者治疗的新标准;抗血管新生药物在NSCLC的治疗疗效得到了进一步证实;EGF疫苗在晚期NSCLC治疗中的结果值得期待。这些成果将会改变目前晚期NSCLC的治疗策略,而基于患者临床特点及分子分型的个体化治疗将成为晚期非小细胞肺癌治疗的新趋势。     

分子靶向药物治疗非小细胞肺癌的策略

目的:介绍分子靶向药物治疗非小细胞肺癌的策略。方法:依据文献综述分子靶向药物治疗非小细胞肺癌的原理、一线及二线用药原则、未来分子靶向治疗药物的研究方向。结果与结论:治疗非小细胞肺癌需设计合理有效的一线及二线靶向治疗措施;未来肿瘤治疗的方向将是针对肿瘤细胞的特定靶点的个体化靶向治疗。     

晚期非小细胞肺癌的中西医结合药物治疗现状

近年来,肺癌在内科药物治疗方面有较大进展,传统化疗、分子靶向药物、靶向药物耐药的后续治疗,以及免疫疗法在晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的综合治疗中扮演着不可替代的角色,但也存在一些不足之处,如化疗及靶向药物的毒副作用和耐药等,5年生存率仍然很低。诸多临床工作者为尽可能的延长晚期NSCLC患者的生存时间、提高患者的生活质量而采用中西医结合的治疗手段,效果明显。该文就晚期非小细胞肺癌的中西医结合药物治疗现状作一综述。     

表皮生长因子受体非突变型非小细胞肺癌分子靶治疗有效1病例报道及相关文献复习

目的：了解表皮生长因子受体（ epidermal growth factor receptor ,EGFR）酪氨酸激酶抑制剂（ EGFR tyrosine kinase inhibitor , EGFR-TKI）对于非EGFR突变的非小细胞肺癌（ non-small cell lung cancer ,NSCLC）的疗效。方法1例化疗后进展的非EGFR突变的非小细胞肺癌肺癌接受EGFR-TKI治疗,靶向治疗后定期复查评价疗效。结果患者接受吉非替尼治疗（250 mg qd）3 w后症状部分缓解（ PR）,4月后KPS提高到90分,化疗后2月及4月复查胸部CT与老片比较达PR。患者目前随访中,病情稳定。结论对于非EGFR基因突变的NSCLC, EGFR-TKI治疗仍然是一种有效治疗手段。     

非小细胞肺癌EGFR-TKIs靶向治疗获得性耐药机制及治疗方案研究进展

近年来,非小细胞肺癌(NSCLC)的发病率和病死率居高不下,临床多采用手术治疗为主,联合化疗、放疗的综合治疗,但对晚期丧失手术机会的患者,靶向治疗带来新的治疗方案,已成为NSCLC精准医学的新方向.靶向药物的应用可显著改善敏感突变的NSCLC患者人群生存质量,但几乎所有靶向药物治疗的NSCLC患者最终均不可避免出现获得...     

Recent advances in targeted therapy for non-small cell lung cancer

Non-small-cell lung cancer (NSCLC) is characterized by wide molecular heterogeneity. In recent years, novel agents that target specific, aberrant molecular pathways in NSCLC have been under rigorous evaluation. Erlotinib, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, improves survival for advanced NSCLC patients who progressed following one or two prior chemotherapy regimens. Novel molecular predictive markers, such as EGFR mutations and gene amplification, are at present under evaluation to select patients for therapy with erlotinib. Another area of progress is the recent demonstration that bevacizumab, a monoclonal antibody against the vascular endothelial growth factor (VEGF), extended survival when administered in combination with chemotherapy for patients with non-squamous NSCLC. Promising anticancer activity has also been noted with agents that inhibit the VEGF receptor tyrosine kinase in patients with advanced NSCLC. Inhibitors of the proteosomal complex, histone deacetylase, mammalian target of rapamycin pathway, and other growth factor receptor-mediated signaling are under investigation for treatment of NSCLC. These developments have paved the way for a new era of tailor-made therapies based on clinical or molecular/genetic profiles in the treatment of NSCLC. This article reviews the recent advances in targeted therapy of advanced NSCLC.     

Recent advances in targeted therapy for non-small cell lung cancer

Non-small-cell lung cancer (NSCLC) is characterized by wide molecular heterogeneity. In recent years, novel agents that target specific, aberrant molecular pathways in NSCLC have been under rigorous evaluation. Erlotinib, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, improves survival for advanced NSCLC patients who progressed following one or two prior chemotherapy regimens. Novel molecular predictive markers, such as EGFR mutations and gene amplification, are at present under evaluation to select patients for therapy with erlotinib. Another area of progress is the recent demonstration that bevacizumab, a monoclonal antibody against the vascular endothelial growth factor (VEGF), extended survival when administered in combination with chemotherapy for patients with non-squamous NSCLC. Promising anticancer activity has also been noted with agents that inhibit the VEGF receptor tyrosine kinase in patients with advanced NSCLC. Inhibitors of the proteosomal complex, histone deacetylase, mammalian target of rapamycin pathway, and other growth factor receptor-mediated signaling are under investigation for treatment of NSCLC. These developments have paved the way for a new era of tailor-made therapies based on clinical or molecular/genetic profiles in the treatment of NSCLC. This article reviews the recent advances in targeted therapy of advanced NSCLC.     

Targeting blood vessels for the treatment of non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Although modest survival benefit has been observed with surgery, radiotherapy and platinum-based chemotherapy, an efficacy plateau has been reached. It has become obvious, therefore, that additional treatments are needed in order to provide an improved survival benefit for these patients. The use of molecular targeted therapies, particularly those against tumor capillaries, has the potential to improve outcomes for NSCLC patients. Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), is the first targeted drug that has shown survival advantage when combined with chemotherapy in NSCLC. Other antivascular agents, including vascular disrupting agents (VDAs) and different small-molecule receptor tyrosine kinase inhibitors, have also shown promise in phase I and II trials in NSCLC. The aim of this study is to describe the clinical properties of these drugs and to discuss the evidence that supports their use in the treatment of NSCLC. Furthermore, we plan to review the main pitfalls of antivascular strategies in NSCLC cancer therapy as well as assess the future direction of these treatment methods with an emphasis on clarifying the molecular background of the effects of these drugs and defining the biomarkers.     

Molecularly-targeted therapies for non-small cell lung cancer

Targeting cell-signalling pathways that confer survival advantage to cancer cells has become a major focus of investigation for the treatment of various malignancies. Non-small cell lung cancer (NSCLC), a disease with wide molecular heterogeneity, has become a main testing ground for the evaluation of various targeted agents. Inhibition of the epidermal growth factor pathway with erlotinib results in improved survival and symptom control for patients with advanced NSCLC who progressed following one or two prior chemotherapy regimens. Gefitinib, the first epidermal growth factor receptor (EGFR) inhibitor to be approved by the FDA, failed to demonstrate survival advantage over placebo in a large Phase III trial for patients with advanced NSCLC. The results of this study have raised several important clinical and biological issues that may be relevant for the development of other targeted agents. Recent identification of mutations in the ATP-binding pocket of the EGFR is the first step towards proper patient selection for therapy with an EGFR tyrosine kinase inhibitor. In addition, predictive potential has also been seen with EGFR gene amplification. It is unclear whether monoclonal antibodies against the EGFR may be active independent of the EGFR mutation, as the site of action is different from tyrosine kinase inhibitors. A recent randomised clinical trial that combined the antiangiogenic agent bevacizumab with chemotherapy has demonstrated survival advantage over chemotherapy alone for certain subsets of patients with advanced NSCLC. The exciting results of this study represent an important advance in the treatment of patients with advanced NSCLC.     

Molecularly-targeted therapies for non-small cell lung cancer

Targeting cell-signalling pathways that confer survival advantage to cancer cells has become a major focus of investigation for the treatment of various malignancies. Non-small cell lung cancer (NSCLC), a disease with wide molecular heterogeneity, has become a main testing ground for the evaluation of various targeted agents. Inhibition of the epidermal growth factor pathway with erlotinib results in improved survival and symptom control for patients with advanced NSCLC who progressed following one or two prior chemotherapy regimens. Gefitinib, the first epidermal growth factor receptor (EGFR) inhibitor to be approved by the FDA, failed to demonstrate survival advantage over placebo in a large Phase III trial for patients with advanced NSCLC. The results of this study have raised several important clinical and biological issues that may be relevant for the development of other targeted agents. Recent identification of mutations in the ATP-binding pocket of the EGFR is the first step towards proper patient selection for therapy with an EGFR tyrosine kinase inhibitor. In addition, predictive potential has also been seen with EGFR gene amplification. It is unclear whether monoclonal antibodies against the EGFR may be active independent of the EGFR mutation, as the site of action is different from tyrosine kinase inhibitors. A recent randomised clinical trial that combined the antiangiogenic agent bevacizumab with chemotherapy has demonstrated survival advantage over chemotherapy alone for certain subsets of patients with advanced NSCLC. The exciting results of this study represent an important advance in the treatment of patients with advanced NSCLC.     

Chemotherapy versus palliative care in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the world's leading cause of cancer death and about 75% of all patients have advanced disease incurable with localized treatments (surgery and radiotherapy) alone. The aims of therapy in these are palliation of symptoms and extension of life. A substantial body of evidence has emerged in the last 15 years which shows that cisplatin-based combination chemotherapy prolongs life in advanced NSCLC. This evidence, which was well summarized in a major meta-analysis published in 1995, indicated that the degree of impact on survival is modest. Hence the balance between survival benefit and treatment-related toxicity is crucial in all considerations of chemotherapy in this disease. More recently this balance has been altered by considerable progress in the reduction of treatment-related toxicity and by documentation of lung cancer symptom palliation by effective chemotherapy. In 1999 a randomized trial of mitomycin, ifosfamide and cisplatin versus palliative care in 351 patients demonstrated a significant survival advantage for those receiving chemotherapy, which did not compromise their quality of life. This review looks forward to further progress employing newer agents both as first- and second-line chemotherapy in advanced NSCLC.     

Targeting tumor cell resistance to apoptosis induction with antisense oligonucleotides: progress and therapeutic potential.

Despite the use of combination chemotherapy and immunotherapy, the survival rate of adult cancer patients has only moderately increased. Diminished apoptosis, due to overexpression of anti-apoptotic proteins, is involved in tumorigenesis and treatment resistance. Antisense oligonucleotides can be used to specifically inhibit unwanted gene expression and hence target the molecular basis of genetic diseases. Recently developed antisense oligonucleotides with the ability to inhibit the expression of anti-apoptotic proteins, including Bcl-2, Bcl-xL, FLIP and surviving, have been shown to facilitate tumor cell apoptosis and sensitize tumor cells to cytotoxic treatments. This suggests their use in combination with conventional treatments as an approach to more effective cancer therapy.     

厄洛替尼单药一线治疗非小细胞肺癌的研究进展

高效低毒的分子靶向治疗药物厄洛替尼,在非小细胞肺癌(NSCLC)的二、三线治疗以及序贯和维持治疗中,已经显示出其能够使患者临床获益.厄洛替尼单药为晚期NSCLC的一线治疗新的选择方案.本文就其在老年、体力状态较差、不吸烟以及存在表皮生长因子(EGFR)敏感性突变或K-ras耐药突变的NSCLC患者中的应用作一综述.     

Neoadjuvant chemotherapy in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is a systemic illness. More than half of those patients who present with stage I-IIIA disease and are resected will experience distant relapse. Postoperative adjuvant chemotherapy has been evaluated in several randomized trials but the results of these trials have been inconclusive with increased survival reported in few trials. In resectable stage IIIA NSCLC the findings of three randomized trials have indicated that the survival of these patients is better with neoadjuvant chemotherapy plus surgical resection than with resection alone. Phase II trials using preoperative concurrent chemoradiotherapy have been carried out with encouraging results. The majority of patients with stage IIIA NSCLC require multimodality therapy if they are to achieve a 5-year survival. Combined modality treatment in locally advanced NSCLC continues to evolve and is a subject of ongoing research. One focus for present research is to integrate new active agents into the neoadjuvant setting. Another challenge is to find better treatment approaches in earlier stages of disease. Some data suggest that induction chemotherapy in stage I-II is feasible, does not appear to compromise surgery and yields high response rates. A further aim is to use molecular biological markers of malignancy to identify patients at highest risk of metastatic relapse.