Precision treatment after resistance to first-generation EGFR-TKI in patients with non-small cell lung cancer / 中华肿瘤杂志

Recently, with the research progress in molecular classification, the treatment of advanced non-small cell lung cancer (NSCLC) has been established as a model of anti-tumor treatment of precision medicine. The discovery of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) has transformed the treatment of NSCLC from platinum based doublet chemotherapy into era of target therapy. EGFR-TKI, such as erlotinib and gefitinib, have been recommended as standard first-line treatment of patients with EGFR mutation. However, acquired resistance, defined as tumor progression after initial response, seems to be an inevitable consequence of this treatment approach. Clinical modes of EGFR-TKI failure are classified into three types: dramatic progression, gradual progression and local progression. A threonine-to-methionine substitution (T790M) in exon 20 of the EGFR gene is the most common mechanism of resistance. Other mechanisms of resistance include MET amplification, epithelial to mesenchymal transition, small cell transformation, and PIK3CA mutation. This brief comment will provide an overview of the complex and heterogeneous problem of acquired resistance to EGFR-TKI therapy in NSCLC, and the clinical treatment options and new targeted drugs overcoming EGFR-TKI acquired resistance.

Optimizing the methods of whole lung cancer RNA-loaded dendritic cells / 中国肺癌杂志

<p><b>BACKGROUND</b>Dendritic cells (DCs) are the unique antigen-presenting cells that can activate naive T lymphocytes. This function is critical for inducing specific immune response. DCs-based vaccines have been used broadly in immunotherapy for many carcinomas. Constructing vaccines by transfecting total tumor RNA into DCs can be done with a few tumor tissues and need not to identify tumor antigens, so it is especially suitable for lung cancer which lacks tumor-specific antigens but has great heterogenicity and weak immunogenicity. Currently, the best transfection stage and method are still indefinite. So, the objective of this study is to explore the best condition of transfecting total RNA extracted from lung cancer tissues into DCs.</p><p><b>METHODS</b>Ten patients with lung cancer were enrolled whose tumor tissues were CEA and MUC1 positive in immunohistochemical staining. Total tumor RNA were extracted by one-step method. Then DCs and T cells were separated and cultured from peripheral blood monocytes and the RNA was transfected into the DCs in different stages with different methods. CEA and MUC1 expression in the transfected DCs were measured by flow cytometry analysis and T cells' proliferation was examined by mixed lymphocyte reaction (MLR).</p><p><b>RESULTS</b>The expression of CEA and MUC1 protein in immature DCs (11.33±2.64, 39.68±7.25) was remarkably higher than that in mature DCs (5.46±1.63, 27.17±4.16) after transfection with total RNA of lung cancer tissues (P < 0.01), and the DCs presented more powerful effects on T cell proliferation. The CEA and MUC1 expression on DCs were significantly higher in electroporation transfection group (20.53±3.64, 65.39± 9.33) than that in lipofection group (11.33±2.64, 39.68±7.25) and passive pulsing transfection group ( 0.91±0.27,18.53±3.26)(P < 0.01), and the DCs in electroporation transfection group presented more powerful effects on stimulating T cell proliferation than the other two groups did.</p><p><b>CONCLUSIONS</b>Transfecting total tumor RNA into immature DCs by using electroporation is a good way to construct DCs-based vaccines for lung cancer and to achieve a higher activity to stimulate T cell proliferation.</p>

Detection and clinical significance of micrometastases in non-small cell lung cancer / 医学研究生学报

Non-small cell lung cancer has a poor prognosis. Many patients who were proved to have none lymph node metastasis still relapse after operation. It may be caused by micrometastases which can′t be detected by conventional pathologic technique. Recently immunocytochemistry and moleculer methods are used to detect micrometastases in the peripheral blood, bone marrow or lymph node near the tumor. But the standard and reliable methods need to be developed and the clinical significance of micrometastases need to be discussed.

Use of CAP,NP,GP in the treatment of patients with non-small cell lung cancer / 医学研究生学报

Objectives: To evaluate the efficacy, toxicity and side effects of CAP (cytoxan, adriamycin, cisplatin), NP(navelbine, cisplatin), GP(gemcitabine, cisplatin) in the treatment of patients with non small cell Lung cancer(NSCLC). Methods:146 patients with NSCLC diagnosed by pathology or cytology were treated with CAP, GP or GP regimen. Results:The overall response rate of the three groups (CAP, NP, GP)were 33.33%, 46.43% and 47.92% respectively. The major toxicity and side effects was bone marrow inhibition and the gastrointestinal reaction. Grade Ⅲ-Ⅳ side effects of CAP group were significant higher than the others. Conclusions:The regimen of navelbine and cisplatin or gemcitabine and cisplatin was more effective and less toxic than cytoxan, adriamycin, cisplatin and cisplatin.