中医药联合CIK细胞及EGFR-TKIs治疗晚期非小细胞肺癌的研究展望
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摘要
当今在综合医学治疗的背景下,随着生物免疫及分子靶向药物的深入研究,晚期非小细胞肺癌的临床疗效也取得了长足进步。但如何增强细胞免疫的杀伤肿瘤细胞作用的同时逆转分子靶向治疗的耐药及毒副反应,这是突破晚期肺癌免疫及靶向治疗瓶颈及进一步提高疗效亟待解决的问题。中医药在晚期肺癌的治疗中发挥着不可替代的作用并日益受到国内外肿瘤界的关注,本文从中医药、细胞因子诱导的杀伤细胞及表皮生长因子受体酪氨酸激酶抑制剂三者相互联合的角度,探讨晚期非小细胞肺癌新的治疗策略。
In the context of the current comprehensive treatment,the clinical efficacy of advanced non- small cell lung cancer( NSCLC) has made great progress with the further development of biological immune and molecular targeted agents. However,it is a burning problem that how to enhance the cell immunity and to reverse the drug resistance and adverse effects of molecular targeted therapy,which is a problem that needs to be solved urgently in the treatment of advanced NSCLC. Traditional Chinese medicine( TCM) plays an irreplaceable role in the treatment of advanced NSCLC. This article is to discuss the new treatment strategy of the advanced NSCLC from the point of view of the combination of TCM,cytokine induced killer( CIK) cell and epidermal growth factor receptor tyrosine kinase inhibitors( EGFR- TKIs).
In the context of the current comprehensive treatment,the clinical efficacy of advanced non- small cell lung cancer( NSCLC) has made great progress with the further development of biological immune and molecular targeted agents. However,it is a burning problem that how to enhance the cell immunity and to reverse the drug resistance and adverse effects of molecular targeted therapy,which is a problem that needs to be solved urgently in the treatment of advanced NSCLC. Traditional Chinese medicine( TCM) plays an irreplaceable role in the treatment of advanced NSCLC. This article is to discuss the new treatment strategy of the advanced NSCLC from the point of view of the combination of TCM,cytokine induced killer( CIK) cell and epidermal growth factor receptor tyrosine kinase inhibitors( EGFR- TKIs).
引文
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[2]Chen W,Zhang S.Annual report on status of cancer in China,2010[J].Chin J Cancer Res,2014,26(1):48-58.
[3]Fukuoka M,Wu YL,Thongprasert S,et al.Biomarker analyses and final overall survival results from a phase III,randomized,open-label,first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia(IPASS)[J].J Clin Oncol,2011,29(21):2866-2874.
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[7]Shi Y,Zhang CJ,Liu XC,et al.The effect of CIK cell on apoptosis of lung cancer cell A549[J].Chin J Med Res,2010,39(5):61-63.
[8]Shi SJ,Wang R,Chen YT,et al.Combining antiangiogenic therapy with adoptive cell immunotherapy exerts better antitumor effects in non-small cell lung cancer models[J].PLo S One,2013,8(6):e65757.
[9]Wu C,Jiang J,Shi L,et al.Prospective study of chemotherapy in combination with cytokine-induced killer cells in patients suffering from advanced non-small cell lung cancer[J].Anticancer Res,2008,28(6B):3997.
[10]Hontscha C,Borck Y,Zhou H.Clinical trials on CIK cells:First report of the international registry on CIK cells(IRCC)[J].J Cancer Res Clin Oncol,2011,137(2):305-310.
[11]Zhou YS,Long SQ,Wu WY,et al.Effect of traditional Chinese medicine combined cytokine induced killer cells treatment on immune state and clinical symptoms in middle-advanced cancer patients[J].Guangdong Medical Journal,2013,34(8):1285-1286.[周宇姝,龙顺钦,吴万垠,等.中药联合细胞因子诱导的杀伤细胞治疗对中晚期肿瘤患者免疫状态和临床症状的影响[J].广东医学,2013,34(8):1285-1286.]
[12]Chai XS,Li LN,He CX,et al.Effect of traditional Chinese medicine combined with CIK cell treatment on quality of life and immune function in patients with advanced cancer[J].Mod Diagn Treat,2012,23(4):224-226.[柴小姝,李柳宁,何春霞,等.中药联合CIK细胞治疗对晚期恶性肿瘤患者生活质量和免疫功能的影响[J].现代诊断与治疗,2012,23(4):224-226.]
[13]Zhao JJ,Pan K,Wang QJ,et al.Effect of anti-asthma chinese medicine chuankezhi on the anti-tumor activity of cytokine-induced killer cells[J].Chin J Cancer,2013,32(10):553-560.
[14]Zheng X,Li XN.23 cases of lung tumor suppression plaster combined with dendritic cells-cytokine induced killer cells in treatment of advanced adenocarcinoma lung cancer[J].J Anhui Tcm Coll Ege,2013,32(6):30-33.[郑心,李雪妮.肺抑瘤膏联合树突状细胞-细胞因子诱导的杀伤细胞治疗晚期肺腺癌23例[J].安徽中医学院学报,2013,32(6):30-33.]
[15]Meng XL,Li HL,Xu YL,et al.70 cases of strengthening and consolidating body resistance method combined with CIK cell adoptive immunotherapy in the treatment of middle-late malignant tumors[J].TCM Res,2013,26(5):19-22.[孟祥林,李海雷,徐玉玲,等.扶正固本法联合CIK细胞过继免疫治疗中晚期恶性肿瘤70例[J].中医研究,2013,26(5):19-22.]
[16]Meng QY,Lv XF,Ren FY,et al.Effect of Oldenlandia polysaccharide gene expression in Bel7402 cells[J].Chin J Gerontolog,2008,13(28):1271-1272.[孟庆宇,吕秀芳,任凤云,等.白花蛇舌草多糖对Be17402细胞基因表达的影响[J].中国老年学杂志,2008,13(28):1271-1272.]
[17]Zhang XJ,Yang SS.Experimental study on the regulating effect of Scutellariabarbata polysaccharide in vivo anti-tumor and immune[J].Asia-Pacific Traditional Medicine,2008,2(4):54-56.[张秀娟,杨姗姗.半枝莲多糖体内抗肿瘤及其免疫调节作用的实验研究[J].亚太传统医药,2008,2(4):54-56.]
[18]Zhang S,Mu XY,Wang HM,et al.Enhancement of the cytotoxic effect of cytokine induced killers by dendritic cells pulsed with astragalus polysaccharides[J].Chin J Immunol,2009,25(2):140-142.[张嵩,牟晓燕,王红梅,等.黄芪多糖诱导的树突状细胞增强CIK细胞的杀伤作用[J].中国免疫学杂志,2009,25(2):140-142.]
[19]Zhang XJ,Ji YB.Studies on immunological pharmacology of fungal polysaccharides[J].J Harbin University of Commerce Natural Sci Edition,2002,18(1):63-65.[张秀娟,季宇彬.真菌多糖的免疫药理作用的研究[J].哈尔滨商业大学学报,2002,18(1):63-65.]
[20]Gridelli C,Rossi A.EURTAC first-line phase III randomized study in advanced non-small cell lung cancer:Erlotinib works also in European population[J].J Thorac Dis,2012,4(2):219-220.
[21]Wu YL,Liao ML,Zhou QH,et al.The consensus of non-small cell lung cancer with small molecular targeted drug resistance[J].J Evidence-Based Med,2013,13(2):65-69.[吴一龙,廖美琳,周清华,等.非小细胞肺癌小分子靶向药物耐药处理共识[J].循证医学,2013,13(2):65-69.]
[22]Koh Y,Kenmotsu H,Serizawa M,et al.Identification of actionable mutations in surgically resected tumor specimens from Japanese patients with non-small cell lung cancer by ultra-deep targeted sequencing[J].J Clin Oncol,2013:31.
[23]Clark GM,Cameron T,Das Gupta-A,et al.Clinical benefit of erlotinib in male smokers in squamous cell NSCLC[J].J Clin Oncol,2006,24(suppl 18):405s.
[24]Zhou YW,Yan LH,Ren SX,et al.Clinical study on the efficacy and safety of erlotinib in treatment of advanced non-small cell lung cancer[J].Tumor,2008,28(9):780-785.[周裕雯,严令华,任胜祥,等.厄洛替尼治疗晚期非小细胞肺癌的临床研究[J].肿瘤,2008,28(9):780-785.]
[25]Mok TS,Wu YL,Thongprasert S,et al.Gefitinib or carboplatinpaclitaxel in pulmonary adenocarcinoma[J].N Engl J Med,2009,361(10):947-957.
[26]Rosell R,Carcereny E,Gervais R,et al.Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer(EURTAC):a multicentre,open-label,randomised phase 3 trial[J].Lancet Oncol,2012,13(3):239-246.
[27]Zhou C,Wu YL,Chen G,et al.Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutationpositive non-small-cell lung cancer(OPTIMAL,CTONG-0802):a multicenter,open-label,randomized,phase 3 study[J].Lancet Oncol,2011,12(8):735-742.
[28]Zhang L,Ma S,Song X,et al.Gefitinib versus placebo as maintenance therapy in patients with locally advanced non-small cell lung cancer(INFORM;C-TONG 0804):a multicentre,doubleblind andomised phase 3 trial[J].Lancet Oncol,2012,13(5):466-475.
[29]Siow Ming Lee,Iftekhar Khan,Sunil Upadhyay,et al.First-line erlotinib in patients with advanced non-small-cell lung cancer unsuitable for chemotherapy(TOPICAL):a double-blind,placebo-controlled,phase3trial[J].Lancet Oncol,2012,13(11):1161-1170.
[30]Costa DB,Kobayashi S,Tenen DG,et al.Pooled analysis of the prospective trials of geitinib monotherapy for EGFR-mutant non-small cell lung cancers[J].Lung Cancer,2007,58(1):95-103.
[31]Oxnard GR,Arcila ME,Chmielecki J,et al.New strategies in overcoming acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in lung cancer[J].Clin Cancer Res,2011,17(17):5530-5537.
[32]Brahmer JR,Lee JW,Traynor AM,et al.Dosing to rash:a phase II trial of the first-line erlotinib for patients with advanced nonsmall-cell lung cancer an Eastern Cooperative Oncology Group Study(E3503)[J].Eur J Cancer,2014,50(2):302-308.
[33]Sequist LV,Waltman BA,Dias-santagata D,et al.Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors[J].Sci Transl,2011,3(75):75ra26.
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