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小细胞肺癌潜在治疗靶点研究进展

施甜甜, 王玉栋

施甜甜, 王玉栋. 小细胞肺癌潜在治疗靶点研究进展[J]. 肿瘤防治研究, 2019, 46(4): 382-386. DOI: 10.3971/j.issn.1000-8578.2019.18.1360
引用本文: 施甜甜, 王玉栋. 小细胞肺癌潜在治疗靶点研究进展[J]. 肿瘤防治研究, 2019, 46(4): 382-386. DOI: 10.3971/j.issn.1000-8578.2019.18.1360
SHI Tiantian, WANG Yudong. Research Progress on Potential Therapeutic Targets of Small Cell Lung Cancer[J]. Cancer Research on Prevention and Treatment, 2019, 46(4): 382-386. DOI: 10.3971/j.issn.1000-8578.2019.18.1360
Citation: SHI Tiantian, WANG Yudong. Research Progress on Potential Therapeutic Targets of Small Cell Lung Cancer[J]. Cancer Research on Prevention and Treatment, 2019, 46(4): 382-386. DOI: 10.3971/j.issn.1000-8578.2019.18.1360

小细胞肺癌潜在治疗靶点研究进展

详细信息
    作者简介:

    施甜甜 (1993-), 女, 硕士, 医师, 主要从事肿瘤内科治疗工作

    通信作者:

    王玉栋, E-mail:wyd_999@126.com

  • 中图分类号: R734.2

Research Progress on Potential Therapeutic Targets of Small Cell Lung Cancer

More Information
  • 摘要:

    小细胞肺癌(SCLC)约占肺癌的15%,致死率高。SCLC的病理、分子生物学机制和临床预后特征与非小细胞肺癌(NSCLC)不尽相同。大多数SCLC表达神经内分泌特征(整合了神经和内分泌特性),其分子机制可能与TP53和RB1的失活,以及包括Notch信号在内的多个信号通路的频繁中断有关。近年来,随着分子机制研究深入和相关的基因工程小鼠模型的开发以及建立患者来源的异种移植物模型的研究进展,为发现SCLC潜在的治疗靶点,改善疗效和预后带来了新希望。

     

    Abstract:

    Small cell lung cancer (SCLC) is a lethal tumor with high incidence and accounts for approximately 15% of lung cancer. It is different from NSCLC in pathological, molecular, biological mechanisms and clinical characteristics. The majority of SCLC have neuroendocrine characteristics including both neuroendocrine and endocrine features. The molecular mechanism may be related to the inactivation of TP53 and RB1, and the disruption of multiple signaling pathways including Notch signaling. In recent years, the comprehensive molecular analyses and the development of genetically engineered mouse models (GEMMs) and patient-derived xenografts (PDXs) have provided new hope for the treatment of SCLC.

     

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  • [1]

    Alexandrov LB, Ju YS, Haase K, et al. Mutational signatures associated with tobacco smoking in human cancer[J]. Science, 2016, 354(6312): 618-22. doi: 10.1126/science.aag0299

    [2]

    George J, Lim JS, Jang SJ, et al. Comprehensive genomic profiles of small cell lung cancer[J]. Nature, 2015, 524(7563): 47-53. doi: 10.1038/nature14664

    [3]

    Gazdar AF, Bunn PA, Minna JD. Small-cell lung cancer: what we know, what we need to know and the path forward[J]. Nat Rev Cancer, 2017, 17(12): 725-37. doi: 10.1038/nrc.2017.87

    [4]

    Borromeo MD, Savage TK, Kollipara RK, et al. ASCL1 and NEUROD1 reveal heterogeneity in pulmonary neuroendocrine tumors and regulate distinct genetic programs[J]. Cell Rep, 2016, 16(5): 1259-72. doi: 10.1016/j.celrep.2016.06.081

    [5]

    Mollaoglu G, Guthrie MR, Böhm S, et al. MYC drives progression of small cell lung cancer to a variant neuroendocrine subtype with vulnerability to Aurora kinase inhibition[J]. Cancer Cell, 2017, 31(2): 270-85. doi: 10.1016/j.ccell.2016.12.005

    [6]

    Takebe N, Miele L, Harris PJ, et al. Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update[J]. Nat Rev Clin Oncol, 2015, 12(8): 445-64. doi: 10.1038/nrclinonc.2015.61

    [7]

    Semenova EA, Nagel R, Berns A, et al. Origins, genetic landscape, and emerging therapies of small cell lung cancer[J]. Genes Dev, 2015, 29(14): 1447-62. doi: 10.1101/gad.263145.115

    [8]

    Shue YT, Lim JS, Sage J. Tumor heterogeneity in small cell lung cancer defined and investigated in pre-clinical mouse models[J]. Transl Lung Cancer Res, 2018, 7(1): 21-31. doi: 10.21037/tlcr

    [9]

    Jahchan NS, Lim JS, Bola B, et al. Identification and Targeting of Long-Term Tumor-Propagating Cells in Small Cell Lung Cancer[J]. Cell Rep, 2016, 16(3): 644-56. doi: 10.1016/j.celrep.2016.06.021

    [10]

    Travis WD, Brambilla E, Burke AP, et al. Introduction to the 2015 world health organization classification of tumors of the lung, pleura, thymus, and heart[J]. J Thorac Oncol, 2015, 10(9): 1240-2. doi: 10.1097/JTO.0000000000000663

    [11]

    Gazdar AF, Savage TK, Johnson JE, et al. The comparative pathology of genetically engineered mouse models for neuroendocrine carcinomas of the lung[J]. J Thorac Oncol, 2015, 10(4): 553-64. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=WK_LWW2017052520120957

    [12]

    McFadden DG, Papagiannakopoulos T, Taylor-Weiner A, et al. Genetic and clonal dissection of murine small cell lung carcinoma progression by genome sequencing[J]. Cell, 2014, 156(6): 1298-311. doi: 10.1016/j.cell.2014.02.031

    [13]

    Chiappori AA, Soliman H, Janssen WE, et al. INGN-225: a dendritic cell-based p53 vaccine (Ad.p53-DC) in small cell lung cancer: observed association between immune response and enhanced chemotherapy effect[J]. Expert Opin Biol Ther, 2010, 10(6): 983-91. doi: 10.1517/14712598.2010.484801

    [14]

    Saunders LR, Bankovich AJ, Anderson WC, et al. A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo[J]. Sci Transl Med, 2015, 7(302): 302ra136. doi: 10.1126/scitranslmed.aac9459

    [15]

    Dylla SJ. Toppling high-grade pulmonary neuroendocrine tumors with a DLL3-targeted trojan horse[J]. Mol Cell Oncol, 2016, 3(2):e1101515. doi: 10.1080/23723556.2015.1101515

    [16]

    Saito M, Shiraishi K, Goto A, et al. Development of targeted therapy and immunotherapy for treatment of small cell lung cancer[J]. Jpn J Clin Oncol, 2018, 48(7): 603-8. doi: 10.1093/jjco/hyy068

    [17]

    Meder L, König K, Ozretić L, et al. NOTCH, ASCL1, p53 and RB alterations define an alternative pathway driving neuroendocrine and small cell lung carcinomas[J]. Int J Cancer, 2016, 138(4): 927-38. doi: 10.1002/ijc.29835

    [18]

    Sun L, He Q, Tsai C, et al. HDAC inhibitors suppressed small cell lung cancer cell growth and enhanced the suppressive effects of receptor-targeting cytotoxins via upregulating somatostatin receptor Ⅱ[J]. Am J Transl Res, 2018, 10(2): 545-53. https://www.researchgate.net/publication/323640544_HDAC_inhibitors_suppressed_small_cell_lung_cancer_cell_growth_and_enhanced_the_suppressive_effects_of_receptor-targeting_cytotoxins_via_upregulating_somatostatin_receptor_II

    [19]

    Fiorentino FP, Tokgün E, Solé-Sánchez S, et al. Growth suppression by MYC inhibition in small cell lung cancer cells with TP53 and RB1 inactivation[J]. Oncotarget, 2016, 7(21): 31014-28. http://cn.bing.com/academic/profile?id=1f591d2e48510c28afc1cb2a0a8a201b&encoded=0&v=paper_preview&mkt=zh-cn

    [20]

    Helfrich BA, Kim J, Gao D, et al. Barasertib(AZD1152), a Small Molecule Aurora B Inhibitor, Inhibits the Growth of SCLC Cell Lines In Vitro and In Vivo[J]. Mol Cancer Ther, 2016, 15(10): 2314-22. doi: 10.1158/1535-7163.MCT-16-0298

    [21]

    Kim DW, Wu N, Kim YC, et al. Genetic requirement for Mycl and efficacy of RNA Pol I inhibition in mouse models of small cell lung cancer[J]. Genes Dev, 2016, 30(11): 1289-99. doi: 10.1101/gad.279307.116

    [22]

    Gadgeel SM. Targeted Therapy and Immune Therapy for Small Cell Lung Cancer[J]. Curr Treat Options Oncol, 2018, 19(11): 53. doi: 10.1007/s11864-018-0568-3

    [23]

    Polley E, Kunkel M, Evans D, et al. Small Cell Lung Cancer Screen of Oncology Drugs, Investigational Agents, and Gene and microRNA Expression[J]. J Natl Cancer Inst, 2016, 108(10). http://cn.bing.com/academic/profile?id=ee949103a84078c6ed9c00a0ee60cf60&encoded=0&v=paper_preview&mkt=zh-cn

    [24]

    Cristea S, Sage J. Is the canonical RAF/MEK/ERK signaling pathway a therapeutic target in SCLC?[J]. J Thorac Oncol, 2016, 11(8): 1233-41. doi: 10.1016/j.jtho.2016.04.018

    [25]

    Kazanets A, Shorstova T, Hilmi K, et al. Epigenetic silencing of tumor suppressor genes: paradigms, puzzles, and potential[J]. Biochim Biophys Acta, 2016, 1865(2): 275-88. http://cn.bing.com/academic/profile?id=13dfffb7a04e5e71489444ed4d7efcac&encoded=0&v=paper_preview&mkt=zh-cn

    [26]

    Poirier JT, Gardner EE, Connis N, et al. DNA methylation in small cell lung cancer defines distinct disease subtypes and correlates with high expression of EZH2[J]. Oncogene, 2015, 34(48): 5869-78. doi: 10.1038/onc.2015.38

    [27]

    Augert A, Zhang Q, Bates B, et al. Small cell lung cancer exhibits frequent inactivating mutations in the histone methyltransferase KMT2D/MLL2: CALGB 151111(Alliance)[J]. J Thorac Oncol, 2017, 12(4): 704-13. http://cn.bing.com/academic/profile?id=5383ba6c48e2cc652198b50b7ef47d53&encoded=0&v=paper_preview&mkt=zh-cn

    [28]

    Faber AC, Farago AF, Costa C, et al. Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer[J]. Proc Natl Acad Sci U S A, 2015, 112(11): E1288-96. doi: 10.1073/pnas.1411848112

    [29]

    Christensen CL, Kwiatkowski N, Abraham BJ, et al. Targeting transcriptional addictions in small cell lung cancer with a covalent CDK7 inhibitor[J]. Cancer Cell, 2014, 26(6): 909-22. doi: 10.1016/j.ccell.2014.10.019

    [30]

    Semenova EA, Kwon MC, Monkhorst K, et al. Transcription factor NFIB is a driver of small cell lung cancer progression in mice and marks metastatic disease in patients[J]. Cell Rep, 2016, 16(3): 631-43. doi: 10.1016/j.celrep.2016.06.020

    [31]

    Minna JD, Johnson JE. Opening a Chromatin Gate to Metastasis[J]. Cell, 2016, 166(2): 275-6. doi: 10.1016/j.cell.2016.06.031

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出版历程
  • 收稿日期:  2018-09-19
  • 修回日期:  2018-12-11
  • 网络出版日期:  2024-01-12
  • 刊出日期:  2019-04-24

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