乳腺癌干细胞的治疗抵抗及其信号通路

国际肿瘤学杂志››2017,Vol. 44››Issue (7): 544-546.doi:10.3760/cma.j.issn.1673-422X.2017.07.017

乳腺癌干细胞的治疗抵抗及其信号通路

童雅兰，韩涛，刘中正，袁钢，梁岩，刘兆喆，谢晓东，岳成山

723000 陕西省汉中市中心医院放射治疗科（童雅兰、岳成山）；沈阳军区总医院全军肿瘤诊治中心肿瘤科（韩涛、刘中正、袁刚、梁岩、刘兆喆、谢晓冬）

收稿日期:2016-12-13出版日期:2017-07-08发布日期:2017-06-20
通讯作者:岳成山 E-mail:yuechs@163.com
基金资助:

中国博士科学基金（2015M582822）

Therapeutic resistance of breast cancer stem cells and its related signaling pathway

Tong Yalan, Han Tao, Liu Zhongzheng, Yuan Gang, Liang Yan, Liu Zhaozhe, Xie Xiaodong, Yue Chengshan

Department of Radiation Oncology, Hanzhong Central Hospital of Shaanxi Province, Hanzhong 723000, China

Received:2016-12-13Online:2017-07-08Published:2017-06-20
Contact:Yue Chengshan E-mail:yuechs@163.com
Supported by:

Postdoctoral Science Foundation of China (2015M582822)

摘要/Abstract

摘要：乳腺癌干细胞是导致乳腺癌治疗失败的主要原因，其在乳腺癌进展及复发耐药过程中发挥重要作用，与乳腺癌的放化疗、内分泌治疗抵抗等密切相关。其转移潜能及治疗抵抗与上皮间质转化及Hedgehog、Wnt、白细胞介素-6/信号传导与转录激活因子3、转化生长因子-β等多种信号通路相关，而针对这些信号通路的部分靶向药物也正进行临床转化研究，有望为乳腺癌的临床治疗提供新的方法。

关键词:乳腺肿瘤,肿瘤干细胞,靶向治疗

Abstract:Breast cancer stem cells (CSCs) are the main causes leading to the failure of treatment of breast cancer and play important roles in the progression of breast cancer and drug resistance, which are closely related to the therapeutic resistance of radiotherapy and chemotherapy, and endocrine therapy. The metastatic potential and therapeutic resistance of CSCs are associated with epithelial mesenchymal transition and Hedgehog, Wnt, interleukin6/signal transduction and tanscriptional activation factor 3, transforming growth factorβ and other signaling pathways. While some of the targeted drugs targeting these signaling pathways are undergoing clinical transformation, which is expected to provide new approach for the clinical treatment of breast cancer.

童雅兰，韩涛，刘中正，袁钢，梁岩，刘兆喆，谢晓东，岳成山. 乳腺癌干细胞的治疗抵抗及其信号通路[J]. 国际肿瘤学杂志, 2017, 44(7): 544-546.

Tong Yalan, Han Tao, Liu Zhongzheng, Yuan Gang, Liang Yan, Liu Zhaozhe, Xie Xiaodong, Yue Chengshan. Therapeutic resistance of breast cancer stem cells and its related signaling pathway[J]. Journal of International Oncology, 2017, 44(7): 544-546.

参考文献

［1］ Plaks V, Kong N, Werb Z. The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells?［J］. Cell Stem Cell, 2015, 16(3): 225-238. DOI: 10.1016/j.stem.2015.02.015. ［2］ AIHajj M, Wicha MS, BenitoHernandez A, et al. Prospective identification of tumorigenic breast cancer cells［J］. Proc Natl Acad Sci USA, 2003, 100(7): 3983-3988. DOI: 10.1073/pnas.0530291100. ［3］ Liu Y, Nenutil R, Appleyard MV, et al. Lack of correlation of stem cell markers in breast cancer stem cells［J］. Br J Cancer, 2014, 110(8): 2063-2071. DOI: 10.1038/bjc.2014.105. ［4］ CharafeJauffret E, Ginestier C, Iovino F, et al. Aldehyde dehydrogenase 1positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer［J］. Clin Cancer Res, 2010, 16(1): 45-55. DOI: 10.1158/1078-0432.CCR-09-1630. ［5］ McDermott SP, Wicha MS. Targeting breast cancer stem cells［J］. Mol Oncol, 2010, 4(5): 404-419. DOI: 10.1016/j.molonc.2010.06.005. ［6］ Wei W, Tweardy DJ, Zhang M, et al. STAT3 signaling is activated preferentially in tumorinitiating cells in claudinlow models of human breast cancer［J］. Stem Cells, 2014, 32(10): 2571-2582. DOI: 10.1002/stem.1752. ［7］ Wei W, Lewis MT. Identifying and targeting tumorinitiating cells in the treatment of breast cancer［J］. Endocr Relat Cancer, 2015, 22(3): R135-155. DOI: 10.1530/ERC-14-0447. ［8］ Fillmore CM, Kuperwasser C. Human breast cancer cell lines contain stemlike cells that selfrenew, give rise to phenotypically diverse progeny and survive chemotherapy［J］. Breast Cancer Res, 2008, 10(2): R25. DOI: 10.1186/bcr1982. ［9］关心, 陆智祥, 杨同华. 肿瘤干细胞的生物学特性及其研究进展［J］. 生命科学, 2014, 26(2): 194200. ［10］ Zhang M, Atkinson RL, Rosen JM. Selective targeting of radiationresistant tumorinitiating cells［J］. Proc Natl Acad Sci USA, 2010, 107(8): 3522-3527. DOI: 10.1073/pnas.0910179107. ［11］ Howell A, Wardley AM. Overview of the impact of conventional systemic therapies on breast cancer［J］. Endocr Relat Cancer, 2005, 12 Suppl 1: S9-S16. DOI: 10.1677/erc.1.01003. ［12］ Dowsett M, Houghton J, Iden C, et al. Benefit from adjuvant tamoxifen therapy in primary breast cancer patients according oestrogen receptor, progesterone receptor, EGF receptor and HER2 status［J］. Ann Oncol, 2006, 17(5): 818-826. DOI: 10.1093/annonc/mdl016. ［13］ Haughian JM, Pinto MP, Harrell JC, et al. Maintenance of hormone responsiveness in luminal breast cancers by suppression of Notch［J］. Proc Natl Acad Sci USA, 2012, 109(8): 2742-2747. DOI: 10.1073/pnas.1106509108. ［14］ Chakrabarty A, Bhola NE, Sutton C, et al. Trastuzumabresistant cells rely on a HER2PI3KFoxOsurvivin axis and are sensitive to PI3K inhibitors［J］. Cancer Res, 2013, 73(3): 1190-1200. DOI: 10.1158/00085472.CAN-12-2440. ［15］ Bakrania AK, Variya BC, Patel SS. Novel targets for paclitaxel nano formulations: hopes and hypes in triple negative breast cancer［J］. Pharmacol Res, 2016, 111: 577-591. DOI: 10.1016/j.phrs.2016.07.023. ［16］ Creighton CJ, Chang JC, Rosen JM. Epithelialmesenchymal transition (EMT) in tumorinitiating cells and its clinical implications in breast cancer［J］. J Mammary Gland Biol Neoplasia, 2010, 15(2): 253260. DOI: 10.1007/s1091101091731. ［17］ Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer［J］. Oncogene, 2010, 29(34): 4741-4751. DOI: 10.1038/onc.2010.215. ［18］ Onishi H, Katano M. Hedgehog signaling pathway as a therapeutic target in various types of cancer［J］. Cancer Sci, 2011, 102(10): 1756-1760. DOI: 10.1111/j.1349-7006.2011.02010.x. ［19］ Borah A, Raveendran S, Rochani A, et al. Targeting selfrenewal pathways in cancer stem cells: clinical implications for cancer therapy［J］. Oncogenesis, 2015, 4: e177. DOI: 10.1038/oncsis.2015.35. ［20］ O′Brien CA, Kreso A, Jamieson CH. Cancer stem cells and selfrenewal［J］. Clin Cancer Res, 2010, 16(12): 3113-3120. DOI: 10.1158/1078-0432.CCR-09-2824. ［21］ Yu H, Jove R. The STATs of cancernew molecular targets come of age［J］. Nat Rev Cancer, 2004, 4(2): 97-105. DOI: 10.1038/nrc1275. ［22］ Iliopoulos D, Hirsch HA, Wang G, et al. Inducible formation of breast cancer stem cells and their dynamic equilibrium with nonstem cancer cells via IL6 secretion［J］. Proc Natl Acad Sci USA, 2011, 108(4): 1397-1402. DOI: 10.1073/pnas.1018898108. ［23］ Thakur R, Trivedi R, Rastogi N, et al. Inhibition of STAT3, FAK and Src mediated signaling reduces cancer stem cell load, tumorigenic potential and metastasis in breast cancer［J］. Sci Rep, 2015, 5: 10194. DOI: 10.1038/srep10194.

[1]	王盈, 刘楠, 郭兵.抗体药物偶联物在转移性乳腺癌治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 364-369.
[2]	王培鑫, 赵军, 徐世红, 姜朝阳, 王小强, 杨红娟.铁死亡相关机制在骨肉瘤中的应用进展[J]. 国际肿瘤学杂志, 2024, 51(5): 308-311.
[3]	萨蔷, 徐航程, 王佳玉.乳腺癌免疫治疗研究进展[J]. 国际肿瘤学杂志, 2024, 51(4): 227-234.
[4]	杨智, 陆以乔, 顾花艳, 丁佳玲, 郭贵龙.肿瘤微环境介导乳腺癌靶向治疗耐药的研究进展[J]. 国际肿瘤学杂志, 2024, 51(4): 235-238.
[5]	张栋岩, 王品, 魏秋亚, 邓成伍, 魏相相, 高远飞, 王琛.索凡替尼靶向联合卡培他滨和奥沙利铂治疗肝内胆管癌术后患者1例及文献复习[J]. 国际肿瘤学杂志, 2024, 51(4): 249-253.
[6]	陈波光, 王苏贵, 张永杰.血清胆碱酯酶与炎症标志物在ⅠA~ⅢA期乳腺癌预后中的作用[J]. 国际肿瘤学杂志, 2024, 51(2): 73-82.
[7]	马正红, 姜超.非小细胞肺癌KRAS^G12C突变的研究进展[J]. 国际肿瘤学杂志, 2024, 51(2): 95-98.
[8]	顾花艳, 朱腾, 郭贵龙.乳房微生物群与乳腺癌：现状与未来[J]. 国际肿瘤学杂志, 2024, 51(1): 55-58.
[9]	王景, 许文婷.中性粒细胞与淋巴细胞比值、癌胚抗原联合凝血指标对直径≤1.0 cm的良恶性乳腺结节鉴别诊断价值研究[J]. 国际肿瘤学杂志, 2023, 50(9): 520-526.
[10]	冯诚天, 黄芙蓉, 曹世玉, 王健宇, 南丁阿比雅思, 姜永冬, 朱娟英.HER2阳性乳腺癌患者HER2表达水平与影像学特征的关系[J]. 国际肿瘤学杂志, 2023, 50(9): 527-531.
[11]	黄辉, 丁江华.靶向FGFR2治疗晚期胆管癌的研究进展[J]. 国际肿瘤学杂志, 2023, 50(9): 569-573.
[12]	冯东旭, 吴炜, 高平发, 王军, 施丽娟, 陈大伟, 李文兵, 张美峰.miR-451通过调控Rho/ROCK1信号通路对乳腺癌细胞糖酵解及凋亡的影响[J]. 国际肿瘤学杂志, 2023, 50(8): 449-456.
[13]	王婷, 李文倩, 解友邦.低氧与急性髓系白血病细胞氧感受通路的相关性[J]. 国际肿瘤学杂志, 2023, 50(8): 503-507.
[14]	李开春, 丁昌利, 于文艳.安罗替尼联合特瑞普利单抗治疗晚期肺肉瘤样癌1例[J]. 国际肿瘤学杂志, 2023, 50(8): 511-512.
[15]	陈秋, 王雷, 王明琦, 张梅.恩沃利单抗联合阿昔替尼治疗肾癌肺转移1例并文献复习[J]. 国际肿瘤学杂志, 2023, 50(7): 445-448.