免疫检查点抑制剂治疗少见突变非小细胞肺癌疗效的研究进展

驱动基因的发现及针对驱动基因的靶向治疗已显著提高了肺癌患者的生存质量和时间,但目前对于BRAF、HER2、MET、RET等少见驱动基因改变肺癌患者的靶向药物的选择仍然较少。近年来免疫检查点抑制剂在肺癌治疗中取得了一定的疗效,但因为少见驱动基因突变的肺癌患者本身样本量少,开展大规模临床随机对照试验尚存在一定的困难,目前此类患者接受免疫检查点抑制剂治疗的疗效情况仍不明确。本文将对目前已掌握的免疫检查点抑制剂治疗BRAF、HER2、MET、RET等少见驱动基因改变肺癌患者的临床研究结果进行综述,以期在一定程度上为临床工作提供一些依据和参考。     

小细胞肺癌的分子靶向治疗现状与展望

小细胞肺癌以侵袭性高、容易出现远处转移而著称,预后极差。化疗是各期小细胞肺癌治疗的基石所在。与化疗相比,分子靶向治疗具有高效、低毒的特点,是目前肿瘤治疗发展的新方向。近年来,一些分子靶向药物在治疗中小细胞肺癌患者治疗中进行了临床研究。本文将对小细胞肺癌分子靶向治疗的重要分子靶点和相应药物进行论述。      

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。     

晚期非小细胞肺癌抗血管生成治疗联合免疫检查点抑制剂的研究进展

近年来,转移性或局部晚期非小细胞肺癌的治疗取得了较大的进展,特别是在一线治疗或治疗后出现进展的患者。通过联合治疗提高疗效已成为该领域的主要研究方向,对于没有驱动基因突变或对靶向治疗无效的患者,这种探索尤为迫切。有证据表明促血管生成因子具有免疫抑制活性,这使得研究人员开始评估抗血管生成药物联合免疫检查点抑制剂治疗晚期非小细胞肺癌的潜在协同作用。本文就抗血管生成药物联合免疫检查点抑制剂治疗晚期非小细胞肺癌的理论基础及临床研究进行综述。     

非小细胞肺癌靶向治疗研究进展

目前肺癌的生物靶向药物抗表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)已成功地应用于肺癌临床治疗.但肺癌分子生物学机制十分复杂,新的生物靶点药物在临床中的重要作用日益受到关注.本文对上述分子生物学标志物在肺癌治疗中的作用及其相关临床研究进展进行综述.     

基于"肺与大肠相表里"理论探讨肺癌靶向药物相关性腹泻与肠道菌群关系的研究进展

在中医中,"肺与大肠相表里"是重要的脏腑相关理论,是中医藏相学说从整体功能状态审视机体生命活动的重要理论之一.随着实验和临床研究涌现,人们对此理论的认识层层深入.目前,该理论在肺癌患者的临床治疗中得到应用,靶向药物治疗所致肠道菌群紊乱的相关性腹泻是晚期肺癌常见的不良反应之一,会严重影响患者的生活质量和治疗效果.本文立足于"肺与大肠相表里"这一理论,对肺癌靶向治疗和肠道菌群的相关性研究进行了总结,以期为肺癌靶向药物性腹泻提供可依据的治疗方法和理论依据.     

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。     

小细胞肺癌靶向治疗的研究进展

摘 要：小细胞肺癌（small cell lung cancer,SCLC）约占全部肺癌的15%~20%,其生物学行为表现为恶性程度高、侵袭性强、预后差。尽管初始治疗时对放、化疗敏感,但小细胞肺癌患者容易早期出现复发转移,因疾病进展后缺乏有效治疗手段,最终导致患者死亡。近十年,靶向治疗的发展给非小细胞肺癌的治疗策略带来了巨大改变。SCLC同样具有大量体细胞突变,针对不同靶点的分子靶向药物在SCLC患者治疗中亦进行了很多探索。虽然目前没有有效的靶向药物被批准用于治疗SCLC,一些新的靶向药物在临床研究中的疗效给SCLC的治疗带来了曙光。全文将对SCLC靶向治疗的研究现状及进展进行综述。     

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。     

TKIs治疗EML4-ALK阳性非小细胞肺癌脑转移的研究进展

摘 要：间变性淋巴瘤激酶（anaplastic lymphoma kinase,ALK）基因重排是非小细胞肺癌（NSCLC）一种新的肿瘤驱动基因,促使肺癌发生和进展。近年来针对ALK融合基因的酪氨酸激酶抑制剂崭露头角,相关药物研究在非小细胞肺癌脑转移治疗中有较大进展,成为靶向治疗的热点。全文就治疗ALK阳性NSCLC脑转移的靶向药物的临床研究作一综述。     

肺癌免疫治疗: 新时代，新思考

[摘要] 近年来,免疫检查点抑制剂不断被研发及其在临床实践中的应用拓展,迅速改变着肺癌的治疗模式。目前,中国研究者也踊跃研发多款免疫治疗药物并将其逐渐应用于临床研究,预示着中国已进入免疫治疗新时代。但随着临床研究的不断拓展及实验数据的不断积累,同时也给我们带来许多新挑战和新思考。本文主要对肺癌免疫治疗模式的突破、免疫治疗临床试验排除的特殊人群、免疫治疗疗效评价、治疗相关不良反应以及疗效预测标志物等多方面发展现状和挑战进行逐一阐述。     

基于CiteSpace的肺癌免疫治疗研究的可视化分析

Objective To understand the current status of research on lung cancer immunotherapy to provide a reference for further investigation and future topic selection in this field. Methods CiteSpace visualization analysis software was used to analyze 400 Chinese studies in CNKI and 5 001 English studies in the Web of Science database from 2005 to 2021, with “lung cancer” and “immunotherapy” as keywords. Keyword co-occurrence analysis was performed on 17 English studies of “Lung Cancer” “Immunotherapy” and “Single cell sequencing” in the Web of Science database. Results “Non-small cell lung cancer” “immunosuppressants” “PD-L1” “dendritic cells” and “cytokine-induced killer cells” are current research hotspots in lung cancer immunotherapy. Monoclonal antibody drugs including nivolumab, pembrolizumab, atezolizumab, and durvalumab are hotspot drugs. Immunotherapy combined with chemotherapy as well as PD-L1 expression have become the focus of continuous research. The majority of studies on lung cancer immunotherapy are conducted in the United States, followed by China. Conclusion Lung cancer immunotherapy has gradually become a research hot spot in China. In the future, in-depth research is needed to provide cutting-edge directions for lung cancer immunotherapy. © 2023, CHINA RESEARCH ON PREVENTION AND TREATMENT. All rights reserved.     

非小细胞肺癌免疫治疗生物标志物研究进展

非小细胞肺癌约占所有肺癌类型的75%~80%,5年生存率仅为15%。近年来人们对肺癌精准治疗的认识明显提高,但非小细胞肺癌的治疗仍面临挑战,驱动基因阴性患者的治疗方式十分有限,晚期患者的预后仍较差。免疫治疗药物可以通过阻断免疫检查点使抗肿瘤T细胞免疫反应恢复或增强,或者T细胞受体转导的T细胞免疫疗法靶向大部分的肿瘤特异性抗原从而起到抗肿瘤作用。目前,仅免疫检查点治疗的临床试验表明,非小细胞肺癌中非选择性人群的客观缓解率为10%~20%,仍有大部分患者不能从免疫治疗中获益,故优势人群的筛选仍十分重要。PD-L1是目前最常用的免疫治疗的疗效预测标志物,但仍存在一定的局限性,不能作为常规标志物应用于临床。另有相关研究表明：肿瘤突变负荷、肿瘤浸润淋巴细胞、微卫星不稳定等都是预测免疫治疗疗效的重要生物标志物。本文将对目前临床研究中关于免疫治疗的相关生物标志物新进展作系统综述。     

多色标记免疫组织化学染色和免疫荧光染色在肺癌免疫治疗中的研究进展

肺癌是目前临床上最常见的恶性肿瘤,严重威胁着患者的生命健康及生活质量。程序性细胞死亡受体1(programmed cell death receptor 1, PD-1)及其配体(programmed cell death ligand 1, PD-L1)抑制剂为非小细胞肺癌(non-small cell lung cancer, NSCLC)患者提供了新的治疗策略。现有的生物标志物检测对准确选择免疫治疗受益的患者均有一定的价值,但都存在着局限性。多标记免疫组织化学/免疫荧光(multiplex immunohistochemistry/immunofluorescence,mIHC/IF)技术允许在单一组织切片上同时检测多个抗体,并对细胞组成、细胞功能和细胞-细胞相互作用进行全面研究。国内外已有大量研究使用mIHC/IF技术对肿瘤免疫微环境(tumor immune microenvironment, TIME)下特异性免疫细胞群进行了探索,发现其有助于肺癌患者临床预后判断及疗效预测。肺癌免疫治疗时代,这项技术在转化研究和临床实践中均具有良好的应用前景。本文就mIHC/IF检测方法在肺癌免疫治疗中的研究进展进行了总结和展望。     

Immunotherapy – new perspective in lung cancer

Lung carcinoma is associated with a high mortality worldwide, being the leading cause of cancer death. It is mainly classified into squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, and small cell lung cancer. However, such malignancy has been increasingly subdivided into histological and molecular subtypes to guide treatment. Therapies can be used in adjuvant and palliative settings. Regarding immunotherapy, it has been widely tested in both first or subsequent palliative lines. In this sense, drugs such as pembrolizumab, nivolumab, atezolizumab, ipilimumab, avelumab, and durvalumab have been assessed in large studies. Some of these trials have also studied these medicines in adjuvant and in maintenance therapy. In recent years, advances in immunotherapy have raised the hope that the unfavorable prognosis observed in several affected individuals can be changed. Immunotherapy has increased the overall survival in squamous NSCLC, non-squamous NSCLC, and small cell lung cancer. However, it has added to the oncology practice some side effects that are unusual in standard chemotherapy and require special clinical support. In order to show how immunotherapy is being applied in the treatment of lung carcinoma, we reviewed the main studies in adjuvant and palliative scenarios. What is the better scheme? What is the better combination? What is the better dose? When should we use immunotherapy? Does programmed cell death ligand 1 expression significantly interfere in immunotherapy efficiency? Some of these questions have already been answered, while others require more investigations.     

Immunotherapy of lung cancer: an update

In Germany lung cancer is the leading cause of cancer-associated death in men. Surgery, chemotherapy and radiation may enhance survival of patients suffering from lung cancer but the enhancement is typically transient and mostly absent with advanced disease; eventually more than 90% of lung cancer patients will die of disease. New approaches to the treatment of lung cancer are urgently needed. Immunotherapy may represent one new approach with low toxicity and high specificity but implementation has been a challenge because of the poor antigenic characterization of these tumors and their ability to escape immune responses. Several different immunotherapeutic treatment strategies have been developed. This review examines the current state of development and recent advances with respect to non-specific immune stimulation, cellular immunotherapy (specific and non-specific), therapeutic cancer vaccines and gene therapy for lung cancer. The focus is primarily placed on immunotherapeutic cancer treatments that are already in clinical trial or well progressed in preclinical studies. Although there seems to be a promising future for immunotherapy in lung cancer, presently there is not standard immunotherapy available for clinical routine.     

New Strategies and Combinations to Improve Outcomes in Immunotherapy in Metastatic Non-Small-Cell Lung Cancer

Immune checkpoint inhibitors have transformed the treatment of metastatic non-small-cell lung cancer, yielding marked improvements in survival and the potential for durable clinical responses. Primary and acquired resistance to current immune checkpoint inhibitors constitute a key challenge despite the remarkable responses observed in a subset of patients. Multiple novel combination immunotherapy and adoptive cell therapy strategies are presently being developed to address treatment resistance. The success of these strategies hinges upon rational clinical trial design as well as careful consideration of the immunologic mechanisms within the variable tumor immune microenvironment (TIME) which underpin resistance to immunotherapy. Further research is needed to facilitate a deeper understanding of these complex mechanisms within the TIME, which may ultimately provide the key to restoring and enhancing an effective anti-tumor immune response. This review aims to provide an introduction to some of the recent and notable combination immunotherapy and cell therapy strategies used in advanced non-small-cell lung cancer (NSCLC), and the rationale for their use based on current understanding of the anti-tumor immune response and mechanisms of resistance within the TIME.     

Research Progress in Immunotherapy of NSCLC With EGFR-Sensitive Mutations

Lung cancer is a malignant tumor with high incidence and mortality across the world. The use of immune checkpoint inhibitors for lung cancer has improved the prognosis of some lung cancer patients to a greater extent and provided a new direction for the clinical treatment of lung cancer. Immunotherapy still has limitations in terms of its appropriate population and adverse reactions. Particularly for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation, there has been no major breakthrough in current immunotherapy. Whether immunotherapy can bring new benefits after drug resistance is induced by tyrosine kinase inhibitor-targeted therapy and whether the combination of immunotherapy with other treatments can improve the prognosis remain to be studied in depth. In this article, we provide a detailed review of the relevant characteristics of the tumor microenvironment of NSCLC with EGFR mutation and the current research on immunotherapy for NSCLC with EGFR mutation.     

抗血管生成药物治疗肺癌脑转移的研究新进展

晚期肺癌脑转移发生率高,预后差.近年来,随着肺癌总体治疗的发展,为晚期肺癌脑转移提供了更多的治疗手段和期待.目前的临床研究提示抗血管生成药物在肺癌脑转移的治疗中占有重要地位,从大分子的单克隆抗体,到泛靶点抗血管药物,再到小分子酪氨酸激酶抑制剂(Tyrosine kinase inhibitor,TKI),均显示出一定的...     

Immunotherapy: is a minor god yet in the pantheon of treatments for lung cancer?

Immunotherapy has been studied for many years in lung cancer without significant results, making the majority of oncologists quite skeptical about its possible application for non-small cell lung cancer treatment. However, the recent knowledge about immune escape and subsequent ‘cancer immunoediting’ has yielded the development of new strategies of cancer immunotherapy, heralding a new era of lung cancer treatment. Cancer vaccines, including both whole-cell and peptide vaccines have been tested both in early and advanced stages of non-small cell lung cancer. New immunomodulatory agents, including anti-CTLA4, anti-PD1/PDL1 monoclonal antibodies, have been investigated as monotherapy in metastatic lung cancer. To date, these treatments have shown impressive results of efficacy and tolerability in early clinical trials, leading to testing in several large, randomized Phase III trials. As these results will be confirmed, these drugs will be available in the near future, offering new exciting therapeutic options for lung cancer treatment.