53个国家批准检测肺癌基因新技术用于临床

肺癌是全球排名第一位的恶性肿瘤。通常分为非小细胞肺癌和小细胞肺癌。研究结果显示,胰岛素受体的家族成员间变性淋巴瘤激酶是非小细胞肺癌的关键启动癌基因。通过对变性淋巴瘤激酶阳性非小细胞肺癌患者的准确诊断,有助于实现肺癌的个体化靶向治疗和提高临床疗效。     

RRM1与非小细胞肺癌的研究进展

肺癌,尤其是非小细胞肺癌是造成癌症患者死亡的重要原因,目前通过分子标志物指导临床个体化化疗是治疗非小细胞肺癌的新趋势。本文综合介绍核苷酸还原酶亚基1(rebonucleotide reduc-tase M 1,RRM1)在非小细胞肺癌的研究现状及前景。     

生物标志物指导下的非小细胞肺癌靶向治疗

 肺癌是最常见的恶性肿瘤之一。分子靶向治疗在21世纪非小细胞肺癌治疗中具有里程碑的意义。基于分子标志检测的靶向治疗更是为肺癌个体化治疗提供了坚实的基础。主要就EGFR突变检测在非小细胞肺癌个体化表皮生长因子受体酪氨酸激酶抑制（EGFR-TKI）一线、二线及维持治疗中的指导意义进行综述。同时介绍EGFR FISH检测在EGFR TKI治疗研究的现状、抗肿瘤血管药物潜在的分子预测标志以及抗EGFR单克隆抗体的个体化治疗现状。     

EMIA—ALK与非小细胞肺癌相关研究进展

EMIA—ALK是新近发现的主要表达于非小细胞肺腺癌中的融合基因,多出现在年轻的轻度吸烟或非吸烟患者中,ALK抑制剂crizotinib治疗EMIA—ALK阳性非小细胞肺癌有很高的应答率,其出现进一步完善了非小细胞肺癌的个体化治疗。     

EML4-ALK与非小细胞肺癌相关研究进展

 EML4-ALK是新近发现的主要表达于非小细胞肺腺癌中的融合基因,多出现在年轻的轻度吸烟或非吸烟患者中, ALK抑制剂crizotinib治疗EML4-ALK阳性非小细胞肺癌有很高的应答率,其出现进一步完善了非小细胞肺癌的个体化治疗。     

β-tubulinⅢ在非小细胞肺癌中的研究进展

肺癌的发病率在常见肿瘤中占首位,非小细胞肺癌已占到肺癌80%左右,且发病率仍在增长。绝大部分患者确诊非小细胞肺癌时已失去手术治疗的最佳时机,因此化疗是治疗晚期非小细胞肺癌的主要手段。经验性化疗方案或不规范的化疗易导致患者耐药性的产生,以至化疗客观有效率低。随着新型抗肿瘤药物问世及分子生物学/基因遗传学的快速发展,已发现β-tubulinⅢ基因的表达水平与非小细胞肺癌化疗及预后密切相关,将可能成为指导个体化治疗、预测预后的重要生物标志物。根据β-tubulinⅢ基因表达水平、药物敏感情况及以β-tubulinⅢ为介导调控其上下游基因等针对个体化的基因治疗、生物免疫治疗、靶向治疗将是肿瘤学研究和临床肿瘤药物治疗的趋势。     

局部晚期非小细胞肺癌多学科综合治疗进展

非小细胞肺癌是发病率和死亡率最高的恶性肿瘤。近几十年来,在流行病学、CT筛查、分期、病理分型、预后判断及个体化治疗方面都有了一定进展。本文综述了局部晚期非小细胞肺癌的治疗进展。     

蛋白指纹图谱与非小细胞肺癌个体化治疗的研究进展

肺癌是全球发病率和死亡率最高的肿瘤,其中约80%为非小细胞肺癌。对于非小细胞肺癌个体化治疗的最大目标和任务就是要通过各种有效方法获得肺癌治疗获益人群的准确信息指导临床治疗。新兴的蛋白质谱技术正为这一探索提供了优良的高通量技术平台。     

生物标志物在非小细胞肺癌中的研究进展

<正>肺癌是世界范围内常见的癌症且是导致癌症患者死亡的主要原因之一[1],非小细胞肺癌(non-small cell lung cancer,NSCLC)占肺癌的80%⁸5%,总体而言,晚期非小细胞肺癌的预后仍然较差,5年生存率不到15%[2]。因此,寻求NSCLC新的治疗手段以及个体化治疗至关重要。当今,NSCLC患者个体化治疗中,利用分子标志物判断预后和指导治疗成为研究热点。通过检测分子标志物指导个体化治疗,能够选择最有效的治疗策略,使疗效最大化,最大程度降低毒性。然而,影响肺癌发病机制的分子生物学机制十分复     

第三代TKIs在EGFR突变非小细胞肺癌中的应用

肿瘤治疗的个体化带来了临床实践变革。近年来,表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）对EGFR阳性突变的非小细胞肺癌显示出良好的抗肿瘤活性。第三代EGFR-TKIs相对于一代EGFR-TKI,显著提高了EGFR突变晚期非小细胞肺癌治疗的有效率、无进展生存期及总生存期,且对脑转移病灶有良好的疗效,对可手术的EGFR突变非小细胞肺癌术后辅助治疗也体现了无病生存获益,在联合放疗应用于局部晚期及晚期寡转移EGFR突变非小细胞肺癌中优势明显。     

Liquid Biopsy Screening for Early Detection of Lung Cancer: Current State and Future Directions

Liquid biopsy (LB) is clinically utilized to detect minute amounts of genetic material or protein shed by cancer cells, most commonly cell free DNA (cfDNA), as a noninvasive precision oncology tool to assess genomic alterations to guide cancer therapy or to detect the persistence of tumor cells after therapy. LB is also being developed as a multi-cancer screening assay. The use of LB holds great promise as a tool to detect lung cancer early. Although lung cancer screening (LCS) with low-dose computed tomography (LDCT) substantially reduces lung cancer mortality in high-risk individuals, the ability of current LCS guidelines to reduce the public health burden of advanced lung cancer through early detection has been limited. LB may be an important tool to improve early lung cancer detection among all populations at risk for lung cancer. In this systematic review, we summarize the test characteristics, including sensitivity and specificity of individual tests, as they pertain to the detection of lung cancer.  We also address critical questions in the use of liquid biopsy for early detection of lung cancer including: 1. How might liquid biopsy be used to detect lung cancer early; 2. How accurate is liquid biopsy in detecting lung cancer early; and 3. Does liquid biopsy perform as well in never and light-smokers compared with current and former smokers.     

Customizing systemic therapy in patients with advanced non-small cell lung cancer

Lung cancer is the leading cause of cancer deaths worldwide. Standard chemotherapy has been shown to improve quality of life and has a modest influence on overall survival. This modest improvement in survival is partly due to the choice of chemotherapy regimens that have been based on prognostic factors such as age, performance status and comorbidities of the patient. This underlines the importance of developing a more personalized therapy for patients with non-small cell lung cancer. Such an approach may reduce the variation in how individual patients respond to medications by tailoring therapies to their genetic profile. In this review we focus on several aspects of customized therapy, looking not only at patient characteristics but also to tumor histology and specific tumor biomarkers.     

非小细胞肺癌个体化治疗：分子标志的现状和未来

尽管非小细胞肺癌（ＮＳＣＬＣ）的治疗已有较大的进展,但总体而言肺癌患者的预后仍然较差。个体化治疗能选择最有效的治疗策略使疗效最大化,最大程度降低毒性。对生物因子能否指导治疗决策的预测是个体化治疗的关键,最终将改善患者预后。基因组学和蛋白质组学研究针对ＮＳＣＬＣ患者的肿瘤组织进行分子检测,为每一个患者提供最有效的治疗。尽管在临床实践中,应用基因组学和蛋白质组学检测技术仍有很大的困难,但新技术的快速发展能克服这些障碍。     

A case of long-term survival with stage IV small cell lung cancer and early-stage central-type squamous cell lung cancer treated by photodynamic therapy

The present report is on a 67-year-old man with stage IV small cell lung cancer and early-stage centrally located squamous cell cancer of the lung. He was diagnosed as small cell lung cancer with multiple metastasis to the ipsilateral lung and was found to have a central-type early-stage squamous cell cancer by bronchoscope. After obtaining a complete response to the small cell lung cancer with chemotherapy and radiotherapy, photodynamic therapy was applied to the squamous cell carcinoma, resulting in complete disappearance of the tumor. Recurrence of small cell cancer occurred at the ipsilateral lung and this patient died of small cell cancer 8 years after initiation of treatment. Post mortem examination confirmed complete disappearance of squamous cell cancer treated by photodynamic therapy. This is a rare case of long-term survival with stage IV small cell lung cancer and early-stage central-type squamous cell lung cancer successfully treated by photodynamic therapy.     

EGFR突变晚期NSCLC患者MDT诊治报道

本文介绍1例表皮生长因子受体(epidermal growth factor receptor,EGFR)突变晚期非小细胞肺癌(non-small-cell lung cancer,NSCLC)接受表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine ki-nase inhibitors,EGFR-TKIs)治疗后,肿瘤疗效不一致,后经过多次多学科讨论,接受综合诊治的经过.该患者通过经皮肺穿刺明确Ⅳ期左肺腺癌伴纵隔肺门淋巴结、双肺及脑转移,基因检测示EGFR 19外显子缺失,一线予以EG-FR-TKIs治疗.疗效考核提示左肺病灶持续有效,但右肺病灶进行性增大.右肺病灶再次活检提示鳞癌,后经化疗及右肺病灶局部放疗,双侧病灶均得到控制.患者经过多次多学科讨论,实现个体化诊疗,为患者带来生存获益.     

Optimization of tumor spheroid model in mesothelioma and lung cancers and anti-cancer drug testing in H2052/484 spheroids

Advanced lung cancers and mesothelioma remain incurable diseases. Despite some promising new therapy strategies, predicting whether an individual patient will be sensitive to a given therapy is challenging. The purpose of this study is to establish and evaluate the efficiency of a three-dimensional spheroid model of human thoracic cancer in predicting the efficacy of drugs.Human mesothelioma and lung tumor spheroids were established from cell lines and primary cells derived from the patient. The growth kinetics and cell viability of microtumors were assessed using spheroid size and intracellular ATP level. The sensitivity of the mesothelioma spheroids to the cisplatin or cisplatin/pemetrexed combination was determined.We determined that studying the kinetics of the spheroid growth for 15 days after seeding 1000 cells/well in a 96-well plate was optimal. Monitoring the growth kinetic and intracellular ATP of spheroids allowed the identification of early changes in spheroid viability. Finally, we validated this model by measuring a dose-dependent reduction in the cell viability of mesothelioma H2052/484 spheroids treated with both first-line treatments, cisplatin and the cisplatin/pemetrexed combination. In conclusion, we have developed a three-dimensional spheroid model of thoracic tumor cells useful for tailoring the medical treatment to the specific characteristics of each patient.     

Discrepancy between the Clinical Image and Pathological Findings of Non-Small Cell Lung Cancer Harboring an Epidermal Growth Factor Receptor Gene Mutation That Was Surgically Resected after Gefitinib Treatment

We herein describe a discrepancy between the clinical image and pathological findings in a non-small cell lung cancer patient with an epidermal growth factor receptor (EGFR) mutation who underwent surgical resection after gefitinib treatment. The patient was a 66-year-old female with c-stage IIIA lung adenocarcinoma harboring an EGFR gene mutation; she was surgically treated after receiving gefitinib. The pathological examination revealed adenocarcinoma, and the pathologically therapeutic effect was considered to be slight or of no response. EGFR T790M mutation and MET amplification were not present. The pathologically therapeutic effect is generally well correlated with the response rate after induction therapy. In this case, there was a discrepancy between the clinical image and pathological findings. Our findings, therefore, raise questions about the role of surgery after EGFR-tyrosine kinase inhibitor treatment.Key words: Gefitinib, Epidermal growth factor receptor, Non-small cell lung cancer, Pathological effect     

Multiple primary malignancies: a report of two cases

The diagnosis of multiple primary malignancies （MPMs） in a patient has been reported rather frequently during the past decade. Here we present two cases with three synchronous primary malignant tumors. The first patient is a 66-year-old male with synchronous colorectal cancer, renal cell carcinoma （RCC） and non-small cell lung cancer （NSCLC）. The second patient is a 64-year-old female with breast cancer, transitional cell carcinoma of the ureter and endometrial cancer. MPMs seem to be diagnosed in a higher incidence than that predicted only by the influence of hazard and, whenever found, they raise questions regarding not only possible common etiologic factors or same pathogenetic mechanisms but also they cause a lot of troubles to both clinicians and patients because the therapeutic options usually become limited.     

miR-130a targets MET and induces TRAIL-sensitivity in NSCLC by downregulating miR-221 and 222

Non-small cell lung cancer (NSCLC) accounts for ～80% of all lung cancers. Although some advances in lung cancer therapy have been made, patient survival is still quite poor. Two microRNAs, miR-221 and miR-222, upregulated by the MET proto-oncogene, have been already described to enhance cell survival and to induce TNF-related apoptosis-inducing ligand (TRAIL) resistance in NSCLC cell lines, through the downregulation of p27(kip1), PTEN and TIMP3. Here, we further investigated this pathway and showed that miR-130a, expressed at low level in lung cancer cell lines, by targeting MET was able to reduce TRAIL resistance in NSCLC cells through the c-Jun-mediated downregulation of miR-221 and miR-222. Moreover, we found that miR-130a reduced migratory capacity of NSCLC. A better understanding of MET-miR-221 and 222 axis regulation in drug resistance is the key in developing new strategies in NSCLC therapy.     

Paraneoplastic syndromes associated with lung cancer

Paraneoplastic syndromes are signs or symptoms that occur as a result of organ or tissue damage at locations remote from the site of the primary tumor or metastases. Paraneoplastic syndromes associated with lung cancer can impair various organ functions and include neurologic, endocrine, dermatologic, rheumatologic, hematologic, and ophthalmological syndromes, as well as glomerulopathy and coagulopathy (Trousseau’s syndrome). The histological type of lung cancer is generally dependent on the associated syndrome, the two most common of which are humoral hypercalcemia of malignancy in squamous cell carcinoma and the syndrome of inappropriate antidiuretic hormone secretion in small cell lung cancer. The symptoms often precede the diagnosis of the associated lung cancer, especially when the symptoms are neurologic or dermatologic. The proposed mechanisms of paraneoplastic processes include the aberrant release of humoral mediators, such as hormones and hormone-like peptides, cytokines, and antibodies. Treating the underlying cancer is generally the most effective therapy for paraneoplastic syndromes, and treatment soon after symptom onset appears to offer the best potential for symptom improvement. In this article, we review the diagnosis, potential mechanisms, and treatments of a wide variety of paraneoplastic syndromes associated with lung cancer.