肿瘤干细胞及肿瘤靶向治疗的研究进展

doi:10.11904/j.issn.1002-3070.2017.06.010

摘要/Abstract

摘要： 研究发现引起肿瘤复发或转移的根源是肿瘤中一少部分具有无限增殖能力的肿瘤干细胞,其在体内长期存在并不断自我更新,使肿瘤快速增殖且侵袭、转移能力增加,药物敏感性减弱,成为临床治疗的难题。因此,深入了解肿瘤干细胞进而寻找抑制肿瘤干细胞的方法对临床靶向治疗肿瘤具有重要意义。本文从肿瘤干细胞的发现过程、生物学特性、鉴别及培养方法等方面进行了阐述,根据其特点总结针对肿瘤干细胞治疗肿瘤的方法,并重点综述抗生素治疗肿瘤干细胞的研究进展。

关键词: 肿瘤干细胞, 复发, 转移, 靶向治疗, 抗生素

Abstract: The root cause of tumor recurrence or metastasis is a small part of the tumor with unlimited proliferation of tumor stem cells,which can exist for a long time and continue to self-renewal causing rapid tumor proliferation and invasion,metastasis capacity,drug sensitivity,eventually resulting in the problem of weakened clinical treatment.Therefore,it is of great importance to in-depth understanding of tumor stem cells and then to seek strategies to suppress tumor stem cells in clinical targeted tumor therapy.In this paper,the discovery process of tumor stem cells,biological characteristics,identification and culture methods were described to summary a variety of methods to inhibit tumor stem cells according to their characteristics so as to treat tumor.Moreover,it focuses on the research progress on antibiotic treatment of cancer stem cells.

Key words: Cancer stem cells, Recurrence, Metastasis, Targeted therapy, Antibiotics

中图分类号:

R730.5

黄倩倩, 马建加, 吴强, 刘彬彬, 沐晓芹, 刘树林审校. 肿瘤干细胞及肿瘤靶向治疗的研究进展[J]. 实用肿瘤学杂志, 2017, 31(6): 533-537.

HUANG Qianqian, MA Jianjia, WU Qiang, LIU Binbin, MU Xiaoqin, LIU Shulin. Research progress on tumor stem cells and tumor targeted therapy[J]. PRACTICAL ONCOLOGY JOURNAL, 2017, 31(6): 533-537.

参考文献

1 DeSantis CE,Lin CC,Mariotto AB,et al.Cancer treatment and survivorship statistics,2014[J].CA Cancer J Clin,2014,64(4):252-271.
2 Tu LC,Foltz G,Lin E,et al.Targeting stem cells-clinical implications for cancer therapy[J].Curr Stem Cell Res Ther,2009,4(2):147-153.
3 Deshmukh A,Deshpande K,Arfuso F,et al.Cancer stem cell metabolism:a potential target for cancer therapy[J].Mol Cancer,2016,15(1):69-78.
4 Rich JN.Cancer stem cells:understanding tumor hierarchy and heterogeneity[J].Medicine(Baltimore),2016,95(1 Suppl 1):2-7.
5 Dean M,Fojo T,Bates S.Tumour stem cells and drug resistance[J].Nat Rev Cancer,2005,5(4):275-284.
6 Reya T,Morrison SJ,Clarke MF,et al.Stem cells,cancer,and cancer stem cells[J].Nature,2001,414(6859):105-111.
7 Bao S,Wu Q,McLendon RE,et al.Glioma stem cells promote radioresistance by preferential activation of the DNA damage response[J].Nature,2006,444(7120):756-760.
8 Li C,Heidt DG,Dalerba P,et al.Identification of pancreatic cancer stem cells[J].Cancer Res,2007,67(3):1030-1037.
9 Bonnet D,Dick JE.Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell[J].Nat Med,1997,3(7):730-737.
10 Al-Hajj M,Wicha MS,Benito-Hernandez A,et al.Prospective identification of tumorigenic breast cancer cells[J].Proc Natl Acad Sci U S A,2003,100(7):3983-3988.
11 Adikrisna R,Tanaka S,Muramatsu S,et al.Identification of pancreatic cancer stem cells and selective toxicity of chemotherapeutic agents[J].Gastroenterology,2012,143(1):234-45 e7.
12 Dalerba P,Dylla SJ,Park IK,et al.Phenotypic characterization of human colorectal cancer stem cells[J].Proc Natl Acad Sci U S A,2007,104(24):10158-10163.
13 Yang ZF,Ho DW,Ng MN,et al.Significance of CD90+ cancer stem cells in human liver cancer[J].Cancer Cell,2008,13(2):153-166.
14 Driessens G,Beck B,Caauwe A,et al.Defining the mode of tumour growth by clonal analysis[J].Nature,2012,488(7412):527-530.
15 Chen J,Li Y,Yu TS,et al.A restricted cell population propagates glioblastoma growth after chemotherapy[J].Nature,2012,488(7412):522-526.
16 Schepers AG,Snippert HJ,Stange DE,et al.Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas[J].Science,2012,337(6095):730-735.
17 Kondo J,Endo H,Okuyama H,et al.Retaining cell-cell contact enables preparation and culture of spheroids composed of pure primary cancer cells from colorectal cancer[J].Proc Natl Acad Sci U S A,2011,108(15):6235-6240.
18 O'Brien CA,Pollett A,Gallinger S,et al.A human colon cancer cell capable of initiating tumour growth in immunodeficient mice[J].Nature,2007,445(7123):106-110.
19 Moitra K,Lou H,Dean M.Multidrug efflux pumps and cancer stem cells:insights into multidrug resistance and therapeutic development[J].Clin Pharmacol Ther,2011,89(4):491-502.
20 Hubbard SA,Gargett CE.A cancer stem cell origin for human endometrial carcinoma?[J].Reproduction,2010,140(1):23-32.
21 Lamb R,Ozsvari B,Lisanti CL,et al.Antibiotics that target mitochondria effectively eradicate cancer stem cells,across multiple tumor types:treating cancer like an infectious disease[J].Oncotarget,2015,6(7):4569-4584.
22 Hemmati HD,Nakano I,Lazareff JA,et al.Cancerous stem cells can arise from pediatric brain tumors[J].Proc Natl Acad Sci U S A,2003,100(25):15178-83.
23 Singh SK,Clarke ID,Terasaki M,et al.Identification of a cancer stem cell in human brain tumors[J].Cancer Res,2003,63(18):5821-5828.
24 Gialmanidis IP,Bravou V,Amanetopoulou SG,et al.Overexpression of hedgehog pathway molecules and FOXM1 in non-small cell lung carcinomas[J].Lung Cancer,2009,66(1):64-74.
25 Malanchi I,Peinado H,Kassen D,et al.Cutaneous cancer stem cell maintenance is dependent on beta-catenin signalling[J].Nature,2008,452(7187):650-653.
26 Katoh M.Networking of WNT,FGF,Notch,BMP,and hedgehog signaling pathways during carcinogenesis[J].Stem Cell Reviews,2007,3(1):30-38.
27 Heddleston JM,Li Z,Lathia JD,et al.Hypoxia inducible factors in cancer stem cells[J].Br J Cancer,2010,102(5):789-795.
28 Reardon DA.Phase II trial of murine ¹³¹I-labeled antitenascin monoclonal antibody 81C6 administered into surgically created resection cavities of patients with newly diagnosed malignant gliomas[J].J Clin Oncol,2002,20(5):1389-1397.
29 Tang R,Faussat AM,Perrot JY,et al.Zosuquidar restores drug sensitivity in P-glycoprotein expressing acute myeloid leukemia(AML)[J].BMC Cancer,2008,8:51-59.
30 Sancho P,Burgos-Ramos E,Tavera A,et al.MYC/PGC-1alpha balance determines the metabolic phenotype and plasticity of pancreatic cancer stem cells[J].Cell Metab,2015,22(4):590-605.
31 Lou H,Dean M.Targeted therapy for cancer stem cells:the patched pathway and ABC transporters[J].Oncogene,2007,26(9):1357-1360.
32 Takehara M,Hoshino T,Namba T,et al.Acetaminophen-induced differentiation of human breast cancer stem cells and inhibition of tumor xenograft growth in mice[J].Biochem Pharmacol,2011,81(9):1124-1135.
33 Massard C,Deutsch E,Soria JC.Tumour stem cell-targeted treatment:elimination or differentiation.[J].Ann Oncol,2006,17(11):1620-1624.
34 Yamashita T,Honda MK,Nakamoto Y,et al.Abstract 4281:Oncostatin M renders epithelial cell adhesion molecule-positive liver cancer stem cells sensitive to 5-fluorouracil by inducing hepatocytic differentiation[J].Cancer Research,2010,70(11):4687-4697.
35 Piccirillo SG,Reynolds BA,Zanetti N,et al.Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells.[J].Nature,2006,444(7120):761-765.
36 Dhodapkar MV.Immunity to stemness genes in human cancer[J].Curr Opin Immunol,2010,22(2):245-250.
37 Wang CH,Chiou SH,Chou CP,et al.Photothermolysis of glioblastoma stem-like cells targeted by carbon nanotubes conjugated with CD133 monoclonal antibody[J].Nanomedicine,2011,7(1):69-79.
38 Gupta PB,Onder TT,Jiang G,et al.Identification of selective inhibitors of cancer stem cells by high-throughput screening[J].Cell,2009,138(4):645-659.
39 Dong TT,Zhou HM,Wang LL,et al.Salinomycin selectively targets′CD133+′cell subpopulations and decreases malignant traits in colorectal cancer lines[J].Ann Surg Oncol,2011,18(6):1797-1804.
40 Zhang GN,Liang Y,Zhou LJ,et al.Combination of salinomycin and gemcitabine eliminates pancreatic cancer cells[J].Cancer Lett,2011,313(2):137-144.
41 Xiao Z,Sperl B,Ullrich A,et al.Metformin and salinomycin as the best combination for the eradication of NSCLC monolayer cells and their alveospheres(cancer stem cells)irrespective of EGFR,KRAS,EML4/ALK and LKB1 status[J].Oncotarget,2014,5(24):12877-12890.
42 Alayev A,Holz MK.mTOR signaling for biological control and cancer[J].J Cell Physiol,2013,228(8):1658-1664.
43 Cai Z,Ke J,He X,et al.Significance of mTOR signaling and its inhibitor against cancer stem-like cells in colorectal cancer[J].Ann Surg Oncol,2014,21(1):179-188.
44 Ju SY,Huang CY,Huang WC,et al.Identification of thiostrepton as a novel therapeutic agent that targets human colon cancer stem cells[J].Cell Death Dis,2015,6(7):e1801.

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