Zhiyong Ma

MicroRNAs: novel biomarkers for lung cancer diagnosis, prediction and treatment.

MicroRNAs (miRNAs) are short non-protein-coding RNAs that post-transcriptionally regulate mRNA expression. A large body of evidence has identified important roles for these regulators in cell proliferation, differentiation, apoptosis and metabolism, as well as activation of oncogenic and antioncogenic signals. Aberrant expression of miRNAs has been found in most human malignancies and is strongly associated with tumorigenesis, prediction, diagnosis, progress, treatment and prognosis. Thus, miRNAs may become an intriguing and promising therapeutic target for many diseases, including cancer. In addition, research into miRNAs may provide insight into the mechanisms underlying tumor occurrence, progression and metastasis. This review summarizes the current knowledge of miRNAs, their roles in lung cancer and avenues for future research.

The genetic variant rs401681C/T is associated with the risk of non-small cell lung cancer in a Chinese mainland population.

Although lung cancer (LC) is a highly environmentally associated disease, genetic factors are also thought to play a role in this disease. In recent years, genome-wide association studies have identified various susceptible genetic regions for LC. Herein, we used high-resolution melting analysis to genotype 2 significant single nucleotide polymorphisms previously reported in Caucasians, that is, rs401681 at 5p15.33 and rs8034191 at 15q25, in a case-control study with 492 LC cases and 486 cancer-free controls in a Chinese population. We found that the rs401681C/T allele in the TERT-CLPTM1L gene was associated with the risk of non-small cell lung cancer [NSCLC; P = 0.012, odds ratio (OR) = 1.29, 95% confidence interval (95%CI) = 1.09-1.50], but was not associated with the risk of small cell lung cancer (P = 0.571, OR = 1.15, 95%CI = 0.82-1.47). However, no significant association was found between rs8034191T/C and LC risk. These results suggest that genetic variants in the TERT-CLPTM1L gene may predispose individuals to be susceptible to LC, particularly NSCLC, in the Chinese population.

Erlotinib-Based Perioperative Adjuvant Therapy for a Case of Unresectable Stage IIIA (N2) Nonsmall Cell Lung Cancer

Treatment of unresectable nonsmall cell lung cancer (NSCLC) remains challenging. The epidermal growth factor receptor tyrosine kinase inhibitors are promising for patients with aberrant epidermal growth factor receptor activation in tumors. However, little is known whether erlotinib alone could benefit patients with advanced NSCLC. Here, the authors reported a case in which erlotinib alone stabilized stage IIIA (N2) NSCLC, leading to curative resection of lung tumors and invaded mediastinal lymph nodes. After lobectomy, the patient was followed up for 11 months without tumor recurrence. They also briefly reviewed recent literatures and discussed the implication of our findings in the treatment of advanced NSCLC.

[Research progresses of albumin-bound paclitaxel in the treatment of non-small cell lung cancer].

众所周知,紫杉醇是非小细胞肺癌(non-small cell lung cancer, NSCLC)化疗中重要的常用化疗药物,其溶 剂为聚氧乙烯蓖麻油/乙醇,这种溶剂型紫杉醇容易产生 严重的过敏反应,从而加重骨髓抑制、神经毒性等,因 此在临床安全方面其使用受到很大限制;另外,溶剂型 紫杉醇抑制白蛋白介导的药物转运,组织利用度较低, 缺乏量效关系,影响合用药物的疗效,严重影响治疗效 果。近些年来,一种新型紫杉醇——白蛋白结合型紫杉 醇(albumin-bound paclitaxel; nab-paclitaxel)脱颖而出, 弥补了溶剂型紫杉醇的各种不利影响,显示出较好的疗 效和安全性。一系列细胞学和动物学研究显示,白蛋 白结合型紫杉醇的独特作用机制体现在抗肿瘤的多个环 节,包括药物转运、药物吸收、药物利用等方面,有助 于紫杉醇发挥最大的功效。目前白蛋白结合型紫杉醇已 通过国家食品药品监督管理局(SFDA)审批在中国上 市,批准其治疗联合化疗失败的转移性乳腺癌以及辅助 化疗6个月内复发的乳腺癌。除此之外,国外研究者还 进行了一些白蛋白结合型紫杉醇在卵巢癌、前列腺癌、 头颈部鳞癌等中的临床研究,均取得了不错的疗效 以及安全性。2009年美国肿瘤学年会(American Society of Clinical Oncology, ASCO)报道了白蛋白结合型紫杉醇 在黑色素瘤、胰腺癌中应用的一系列I/II期临床研究, 结果令人欣喜,有望成为该两种化疗不敏感肿瘤的有效 药物,并且提示富含半胱氨酸的酸性分泌蛋白(secreted protein acidic and rich in cysteine, SPARC)阳性的患者缓解 率更高、无进展生存时间(progression-free survival, PFS) 更长。目前,肺癌发病率及死亡率居高不下,国外学 者对白蛋白结合型紫杉醇在NSCLC治疗中的应用进行了 很多临床研究。本文将对白蛋白结合型紫杉醇在NSCLC 中应用的最新临床研究做一综述。

Single nucleotide polymorphisms of casitas B-lineage lymphoma proto-oncogene-b predict outcomes of patients with advanced non-small cell lung cancer after first-line platinum based doublet chemotherapy

Background Casitas B-lineage lymphoma proto-oncogene-b (CBLB) influences the threshold of T cell activation and controlling peripheral T cell tolerance. In the present study, we hypothesize that potentially functional single nucleotide polymorphisms (SNPs) in CBLB are associated with clinical outcomes in patients advanced non-small cell lung cancer (NSCLC) treated with the first-line chemotherapy. Methods We genotyped three SNPs (rs2305035, rs3772534 and rs9657904) at CBLB in 116 advanced NSCLC patients with progression free survival (PFS) data and 133 advanced NSCLC patients with overall survival (OS) data, and we assessed their associations, 95% confidence interval (CI), with clinical outcomes by using Cox proportional hazards regression analyses. In silico functional analysis was also performed for the SNPs under investigation. Results We found that associations between the three SNPs and PFS/OS were not significant in the overall NSCLC patients. The rs2305035 AA genotype was associated with a worse PFS in female patients and those of non-smokers or light smokers (95% CI, 1.14-11.81, P=0.030; 95% CI, 1.42-10.24, P=0.008; and 95% CI, 1.39-9.93, P=0.009; respectively), compared with the GG+AA genotypes. We also found that the rs9657904 CC genotype was significantly associated with a worse OS than TT + TC genotypes in male advanced NSCLC patients. Further in silico functional analysis revealed that the rs965704 T allele was significantly associated with lower mRNA expression levels of the CBLB gene. Conclusions Our findings identified two CBLB SNPs (rs2305035 and rs9657904) that were significantly associated with PFS and OS in several subgroups of Chinese advanced NSCLC patients after the first-line chemotherapy.

Mutation abundance affects the therapeutic efficacy of EGFR-TKI in patients with advanced lung adenocarcinoma: A retrospective analysis

ABSTRACT Purpose: To investigate the influence of mutation abundance and sites of epidermal growth factor receptor (EGFR) on therapeutic efficacies of EGFR-tyrosine kinase inhibitor (EGFR-TKIs) treatments of patients with advanced non-small cell lung carcinoma (NSCLC). Methods: EGFR mutational sites and mutation abundance were analyzed by amplification refractory mutation system (ARMS) in paraffin-embedded tissue sections taken from primary or metastatic tumors of 194 NSCLC patients. Results: The median progression-free survival (PFS) time of the enrolled patients was 9.3 months (95% CI, 8.2–10.8 months). The PFS was significantly different with EGFR gene mutation abundance after EGFR-TKI therapy (P = 0.014). The median PFS was significantly longer when the cut-off value of EGFR mutation abundance of exon 19 or exon 21, and solely exon 19 was > 26.7% and 61.8%, respectively. For patients who received EGFR-TKI as first-line treatment, the median PFS was significantly longer in the high mutation abundance group than in the low mutation abundance group (12.7 vs 8.7 months, P = 0.002). Conclusion: The PFS benefits were greater in patients with a higher abundance of exon 19 deletion mutations in the EGFR gene after EGFR-TKI treatment and first line EGFR-TKI treatment led to improved PFS in high mutation abundance patients.

[Recent Advances and Prospect of Advanced Non-small Cell Lung Cancer Targeted Therapy: Focus on Small Molecular Tyrosine Kinase Inhibitors].

At present the treatment of advanced non-small cell lung cancer enters a targeted era and develops rapidly. New drugs appear constantly. Small molecular tyrosine kinase inhibitors have occupied the biggest piece of the territory, which commonly have a clear biomarker as predictor, and show remarkable effect in specific molecular classification of patients. The epidermal growth factor tyrosine kinase inhibitors such as gefitinib, erlotinib, icotinib and anaplastic lymphoma kinase tyrosine kinase inhibitors crizotinib have brought a milestone advance. In recent years new generations of tyrosine kinase inhibitors have achieved a great success in patients with acquired resistance to the above two kinds of drugs. At the same time new therapeutic targets are constantly emerging. So in this paper, we reviewed and summarized the important drugs and clinical trails on this topic, and made a prospect of the future development.

[The role of adjuvant chemotherapy in operable non-small cell lung cancer].

Postoperative recurrence is the main cause of primary treatment failure in the resectable non-small cell lung cancer (NSCLC). Systematic treatments should be taken to decrease the recurrence. Adjuvant chemotherapy, including neoadjuvant chemotherapy, postoperative adjuvant chemotherapy and targeted therapy, is a widely used in this area. In this review, we summarize the clinical trials and meta-analysis related to the adjuvant chemotherapy and targeted therapy in patients with early stage NSCLC.