人源性异种移植模型在胰腺癌个体化治疗研究中的应用

doi:10.3969/j.issn.1674-5817.2019.06.014

实验动物与比较医学 ›› 2019, Vol. 39 ›› Issue (6): 499-504.DOI: 10.3969/j.issn.1674-5817.2019.06.014

• 综述 • 上一篇

人源性异种移植模型在胰腺癌个体化治疗研究中的应用

胡斌权^1,2, 储海盟^1,2, 师长宏²

1.94895部队卫生队, 漳州 363000;
2.空军军医大学实验动物中心, 西安 710032

收稿日期:2019-05-06 出版日期:2019-12-25 发布日期:2021-01-05
作者简介:胡斌权(1995-), 男, 本科, 医师. 研究方向: 动物模型的制备。E-mail: binquanfmmu@163.com
基金资助:
国家自然科学基金资助(31772546)

Application of Patient-Derived Xenograft Models for Personalized Treatment of Pancreatic Cancer

HU Bin-quan^1,2, CHU Hai-meng^1,2, SHI Chang-hong²

1. 94895 Force Health Team, Zhangzhou 363000, China;
2. Airforce Military Medical University Laboratory Animal Center, Xi'an 710032, China

Received:2019-05-06 Online:2019-12-25 Published:2021-01-05

摘要/Abstract

摘要： 本文介绍了胰腺癌人源性异种移植(patient-derived xenograft,PDX)模型的基本特征、建模方法及模型应用中存在的问题,阐述了PDX模型在胰腺癌个体化药物筛选和耐药机制研究中的可行性。常规的胰腺癌标准化疗方案及联合用药疗效低下,因此,需要关注靶向重塑胰腺癌微环境抗肿瘤研究的重要性以期为研究者们提供新的思路,合理地使用该模型开展胰腺癌的研究,为胰腺癌患者提供更加高效的个体化治疗方案。

关键词: 胰腺癌, 人源性异种移植(PDX)模型, 免疫治疗, 肿瘤微环境

Abstract: This paper introduces the basic characteristics and problems in modeling and the application of patient-derived xenograft (PDX) models for pancreatic cancer,and expounds the feasibility of PDX models in the study of individualized drug screening and drug resistance mechanism of pancreatic cancer. Conventional standard chemotherapy and combination therapy regimens for pancreatic cancer are less effective. Therefore, it is necessary to pay attention to the importance of targeting and remodeling the anti-tumor study of pancreatic cancer microenvironment so that it can provide new ideas for researchers, reasonably use this model to carry out pancreatic cancer research,and provide more efficient personalized treatment for patients with pancreatic cancer.

Key words: Pancreatic cancer, Patient-derived xenograft (PDX) models, Immunotherapy, Tumor microenvironment

中图分类号:

Q95-33

胡斌权, 储海盟, 师长宏. 人源性异种移植模型在胰腺癌个体化治疗研究中的应用[J]. 实验动物与比较医学, 2019, 39(6): 499-504.

HU Bin-quan, CHU Hai-meng, SHI Chang-hong. Application of Patient-Derived Xenograft Models for Personalized Treatment of Pancreatic Cancer[J]. Laboratory Animal and Comparative Medicine, 2019, 39(6): 499-504.

参考文献

[1] Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2019[J]. CA Cancer J Clin, 2019, 69(1):7-34.
[2] Kamisawa T, Wood LD, Itoi T, et al.Pancreatic cancer[J]. Lancet, 2016, 388(10039):73-85.
[3] Mohammed A, Janakiram NB, Madka V, et al.Current challenges and opportunities for chemoprevention of pancreatic cancer[J]. Curr Med Chem, 2018, 25(22):2535-2544.
[4] Tsai S, Evans DB.Therapeutic advances in localized pancreatic cancer[J]. JAMA Surg, 2016, 151(9):862-868.
[5] Neoptolemos JP, Kleeff J, Michl P, et al.Therapeutic developments in pancreatic cancer: current and future perspectives[J]. Nat Rev Gastroenterol Hepatol, 2018, 15(6):333-348.
[6] Cho SY, Kang W, Han JY, et al.An integrative approach to precision cancer medicine using patient-derived xenografts[J]. Mol Cells, 2016, 39(2):77-86.
[7] Zhang YJ, Wen CL, Qin YX, et al.Establishment of a human primary pancreatic cancer mouse model to examine and investigate gemcitabine resistance[J]. Oncol Rep, 2017, 38(6):3335-3346.
[8] Guan Z, Lan H, Sun D, et al.A potential novel therapy for FGFR1-amplified pancreatic cancer with bone metastasis, screened by nextgeneration sequencing and a patient derived xenograft model[J]. Oncol Lett, 2019, 17(2):2303-2307.
[9] Guan Z, Lan H, Chen X, et al.Individualized drug screening based on next generation sequencing and patient derived xenograft model for pancreatic cancer with bone metastasis[J]. Mol Med Rep, 2017, 16(4):4784-4790.
[10] Dai W, Liu J, Li Q, et al.A comparison of next-generation sequencing analysis methods for cancer xenograft samples[J]. J Genet Genomics, 2018, 45(7):345-350.
[11] 张贺, 张彩勤, 赵勇, 等. 胰腺癌患者临床特征与异种移植模型的相关性[J]. 实验动物科学, 2018, 35(3):46-51.
[12] Lipner MB, Marayati R, Deng YM, et al.Metformin treatment does not inhibit growth of pancreatic cancer patient-derived xenografts[J]. PLoS One, 2016, 11(1):e014711311.
[13] Xiang J, Hu Q, Qin Y, et al.TCF7L2 positively regulates aerobic glycolysis via the EGLN2 /HIF-1α axis and indicates prognosis in pancreatic cancer[J]. Cell Death Dis, 2018, 9(3):321.
[14] 胡斌权, 陈城明, 张同弟, 等. 人体肿瘤PDX移植模型的优与劣[J]. 实验动物科学, 2015, 32(5):59-62.
[15] Hernandez MC, Bergquist JR, Leiting JL, et al.Patient-derived xenografts can be reliably generated from patient clinical biopsy specimens[J]. J Gastrointest Surg,2019, 23(4):818-824.
[16] Allaway RJ, Fischer DA, de Abreu FB, et al. Genomic characterization of patient-derived xenograft models established from fine needle aspirate biopsies of a primary pancreatic ductal adenocarcinoma and from patient-matched metastatic sites[J]. Oncotarget, 2016, 7(13):17087-17102.
[17] 张贺, 陈薛, 张彩勤, 等. 基于胰腺癌患者来源异种移植模型的化疗药物筛选[J]. 中国实验动物学报, 2018, 26(1):29-35.
[18] Gambara G, Gaebler M, Keilholz U, et al.From chemotherapy to combined targeted therapeutics: in vitro and in vivo models to decipher intra-tumor heterogeneity[J]. Front Pharmacol, 2018, 9(77):1-18.
[19] Sereti E, Karaqianellou T, Kotsoni L, et al.Patient Derived Xenografts (PDX) for personalized treatment of pancreatic cancer: emerging allies in the war on a devastating cancer?[J]. J Proteomics, 2018, 30(118):107-118.
[20] Hiroshima Y, Zhang Y, Zhang N, et al.Patient-derived orthotopic xenograft (PDOX) nude mouse model of soft-tissue sarcoma more closely mimics the patient behavior in contrast to the subcutaneous ectopic model[J]. Anticancer Res, 2015, 35(2):697-701.
[21] 师长宏. 肿瘤患者来源的异种移植(PDX)模型[J]. 实验动物与比较医学, 2018, 38(3):165-168.
[22] Hino A, Yoshida H, Tada Y, et al.Changes from imatinib mesylate to second generation tyrosine kinase inhibitors improve renal impairment with imatinib mesylate in chronic myelogenous leukemia[J]. Int J Hematol, 2016, 104(5):605-611.
[23] Witkiewicz AK, Balaji U, Eslinger C, et al.Integrated patient-derived models delineate individualized therapeutic vulnerabilities of pancreatic cancer[J]. Cell Rep, 2016, 16(7):2017-2031.
[24] Liu X, Meltzer SJ.Gastric cancer in the era of precision medicine[J]. Cell Mol Gastroenterol Hepatology, 2017, 3(3):348-358.
[25] 卓萌, 焦锋, 王理伟, 等. 胰腺癌微环境治疗策略的进展与思考[J]. 中国肿瘤临床, 2018, 45(6):271-276.
[26] Li X, Lee Y, Kang Y, et al.Hypoxia-induced autophagy of stellate cells inhibits expression and secretion of lumican into microenvironment of pancreatic ductal adenocarcinoma[J]. Cell Death Differ, 2019, 26(2):382-393.
[27] Li X, Truty MA, Kang Y, et al.Extracellular lumican inhibits pancreatic cancer cell growth and is associated with prolonged survival after surgery[J]. Clin Cancer Res, 2014, 20(24):6529-6540.
[28] Brown CE, Alizadeh D, Starr R, et al.Regression of glioblastoma after chimeric antigen receptor T cell therapy[J]. N Engl J Med, 2016, 375(26):2561-2569.
[29] Jiang H, Song B, Wang P, et al.Efficient growth suppression in pancreatic cancer PDX model by fully human anti-mesothelin CAR-T cells[J]. Protein Cell, 2017, 8(12):926-931.
[30] Cao R, Song W, Ye C, et al.Internal enhancement of DNA damage by a novel bispecific antibody-drug conjugate-like therapeutics via blockage of mTOR and PD-L1 signal pathways in pancreatic cancer[J]. Cancer Med, 2019, 8(2):643-655.
[31] Gerber MH, Underwood PW, Judge SM, et al.Local and systemic cytokine profiling for pancreatic ductal adenocarcinoma to study cancer cachexia in an era of precision medicine[J]. Int J Mol Sci, 2018, 19(12):1-14.
[32] Chernenko E, Meir J, Bedi A, et al.Patient-derived xenografts as tools in pharmaceutical development[J]. Clin Pharmacol Ther, 2016, 99(6):612-621.
[33] 刘宏飞, 陈晓红, 黄志刚, 等. 类器官和人源性肿瘤组织异种移植模型在肿瘤研究中的应用[J]. 中国比较医学杂志, 2019, 29(3):103-108.
[34] Moreira L, Bakir B, Chatterji P, et al.Pancreas 3D organoids:current and future aspects as a research platform for personalized medicine in pancreatic cancer[J]. Cell Mol Gastroenterol Hepatol, 2018, 5(3):289-298.
[35] Perales-Pat n J, Pi eiro-Ya ez E, Tejero H, et al. Pancreas cancer precision treatment using avatar mice from a bioinformatics perspective[J]. Public Health Genomics, 2017, 20(2):81-91.
[36] Prasad V.Perspective:The precision-oncology illusion[J].Nature, 2016, 537(7619):S63.
[37] Tannock IF, Hickman JA.Limits to personalized cancer medicine[J]. N Engl J Med, 2016, 375(13):1289-1294.
[38] 胡斌权, 曹博, 师长宏. 胃癌人源性异种移植模型制备中的问题与策略[J]. 中国实验动物学报, 2017, 25(6):643-647.

人源性异种移植模型在胰腺癌个体化治疗研究中的应用

Application of Patient-Derived Xenograft Models for Personalized Treatment of Pancreatic Cancer

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