Recent advances in the application of patient-derived tumor xenograft models in prostate cancer

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Author: Jian-Li DUAN 1 Zheng CHEN 2, 3 Yu-Zhuo WANG 3

Affiliation: 1. Department of Urology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China 2. Department of Urology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China 3. Department of Urologic Sciences, University of British Columbia, Vancouver Prostate Centre, Vancouver V5Z1M9, BC, Canada

Keywords: Prostate cancer PDX model Preclinical research Precision medicine


Reference:Duan JL, Chen Z, Wang YZ. Recent advances in the application of patient-derived tumor xenograft models in prostate cancer[J]. Yixue Xinzhi Zazhi, 2021, 31(4): 285-293. DOI: 10.12173/j.issn.1004-5511.202105011.[Article in Chinese]

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Prostate cancer (PCa) is one of the most common male reproductive tumors. If the tumor characteristics, treatment and prognosis can be accurately predicted through in vivo and in vitro experiments, it will greatly reduce unnecessary pain for patients. The patient-derived tu-mor xenografts (PDX) models which are widely used in preclinical and precision medicine re-search, can directly transplant tumors from different individuals into immunodeficient mice. This article will introduce the development, construction and application of the PCa PDX model in detail.

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1.Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660.

2.Liu X, Yu C, Bi Y, et al. Trends and age-period-cohort effect on incidence and mortality of prostate cancer from 1990 to 2017 in China[J]. Public Health, 2019, 172: 70-80. DOI: 10.1016/j.puhe.2019.04.016.

3.邓通, 蔡林, 陈征, 等. 1990年与2017年中国前列腺癌疾病负担分析 [J]. 医学新知, 2020, 30(4): 252-259.DOI: 10.12173/j.issn.1004-5511.2020.04.01. [Deng T, Cai L, Chen Z, et al. Analysis of the burden of prostate cancer in China in 1990 and 2017[J]. Yixue Xinzhi Zazhi, 2020, 30(4): 252-259.]

4.Buzzoni C, Auvinen A, Roobol MJ, et al. Metastatic prostate cancer incidence and pros-tate-specific antigen testing: new insights from the european randomized study of screening for prostate cancer[J]. Eur Urol, 2015, 68(5): 885-890. DOI: 10.1016/j.eururo.2015.02.042.

5.Mullane SA, Van Allen EM. Precision medicine for advanced prostate cancer[J]. Curr Opin Urol, 2016, 26(3): 231-239. DOI: 10.1097/mou.0000000000000278.

6.Sternberg CN, Beltran H. Prostate cancer in 2016: improved outcomes and precision medi-cine come within reach[J]. Nat Rev Urol, 2017, 14(2): 71-72. DOI: 10.1038/nrurol.2016.270.

7.Joshi A, Roberts MJ, Alinezhad S, et al. Challenges, applications and future directions of pre-cision medicine in prostate cancer - the role of organoids and patient-derived xenografts[J]. BJU Int, 2020, 126(1): 65-72. DOI: 10.1111/bju.15103.

8.Wang YZ, Dong L, Gout PW. Patient-derived xenograft models of human cancer[M]. Salt Lake City: Molecular and Translational Medicine, 2018.

9.Gock M, Kühn F, Mullins CS, et al. Tumor take rate optimization for colorectal carcinoma pa-tient-derived xenograft models[J]. Biomed Res Int, 2016, 2016: 1715053. DOI: 10.1155/2016/1715053.

10.Lawrence MG, Taylor RA, Toivanen R, et al. A preclinical xenograft model of prostate cancer using human tumors [J]. Nat Protoc, 2013, 8(5): 836-848. DOI: 10.1038/nprot. 2013.043.

11.Schroeder FH, Okada K, Jellinghaus W, et al. Human prostatic adenoma and carcinoma. Transplantation of cultured cells and primary tissue fragments in "nude" mice [J]. Invest Urol, 1976, 13(6): 395-403. DOI: 10.1007/BF02082098.

12.Giovanella BC, Fogh J. The nude mouse in cancer research[J]. Adv Cancer Res, 1985, 44: 69-120. DOI: 10.1016/s0065-230x(08)60026-3.

13.Pla M, Mahouy G. The SCID mouse[J]. Nouv Rev Fr Hematol, 1991, 33(6): 489-491.

14.Priolo C, Agostini M, Vena N, et al. Establishment and genomic characterization of mouse xenografts of human primary prostate tumors[J]. Am J Pathol, 2010, 176(4): 1901-1913. DOI: 10.2353/ajpath.2010.090873.

15.Toivanen R, Frydenberg M, Murphy D, et al. A preclinical xenograft model identifies castra-tion-tolerant cancer-repopulating cells in localized prostate tumors[J]. Sci Transl Med, 2013, 5(187): 187ra171. DOI: 10.1126/scitran slmed.3005688.

16.Pretlow TG, Wolman SR, Micale MA, et al. Xenografts of primary human prostatic carcino-ma[J]. J Natl Cancer Inst, 1993, 85(5): 394-398. DOI: 10.1093/jnci/85.5.394.

17.Klein KA, Reiter RE, Redula J, et al. Progression of metastatic human prostate cancer to an-drogen independence in immunodeficient SCID mice[J]. Nat Med, 1997, 3(4): 402-408. DOI: 10.1038/nm0497-402.

18.Cunningham D, Zhang Q, Liu S, et al. Interleukin-17 promotes metastasis in an immunocom-petent orthotopic mouse model of prostate cancer[J]. Am J Clin Exp Urol, 2018, 6(3): 114-122. 

19.Fu X, Guadagni F, Hoffman RM. A metastatic nude-mouse model of human pancreatic cancer constructed orthotopically with histologically intact patient specimens [J]. Proc Natl Acad Sci U S A, 1992, 89(12): 5645-5649.DOI: 10.1073/pnas.89.12.5645.

20.Wang Y, Revelo MP, Sudilovsky D, et al. Development and characterization of efficient xeno-graft models for benign and malignant human prostate tissue[J]. The Prostate, 2005, 64(2): 149-159. DOI: 10.1002/pros.20225.

21.Wang Y, Wang JX, Xue H, et al. Subrenal capsule grafting technology in human cancer mod-eling and translational cancer research[J]. Differentiation, 2016, 91(4-5): 15-19.DOI: 10.1016/j.diff.2015.10.012.

22.Lawrence MG, Pook DW, Wang H, et al. Establishment of primary patient-derived xenografts of palliative TURP specimens to study castrate-resistant prostate cancer[J]. The Prostate, 2015, 75(13): 1475-1483. DOI: 10.1002/pros.23039.

23.Shi C, Chen X, Tan D. Development of patient-derived xenograft models of prostate cancer for maintaining tumor heterogeneity[J]. Transl Androl Urol, 2019, 8(5): 519-528.DOI: 10.21037/tau.2019.08.31.

24.Lin D, Wyatt AW, Xue H, et al. High fidelity patient-derived xenografts for accelerating pros-tate cancer discovery and drug development[J]. Cancer Res, 2014, 74(4): 1272-1283. DOI: 10.1158/0008-5472.can-13-2921-t.

25.Pretlow TG, Delmoro CM, Dilley GG, et al. Transplantation of human prostatic carcinoma into nude mice in Matrigel[J]. Cancer research, 1991, 51(14): 3814-3817. DOI: 10.1002/1097-0142(19910715)68:2<451::AID-CNCR2820680241>3.0.CO;2.

26.Harrison RK. Phase II and phase III failures: 2013-2015[J]. Nat Rev Drug Discov, 2016, 15(12): 817-818.DOI: 10.1038/nrd.2016.184.

27.Vaeteewoottacharn K, Pairojkul C, Kariya R, et al. Establishment of highly transplantable cholangiocarcinoma cell lines from a patient-derived xenograft mouse model[J]. Cells, 2019, 8(5): 889-908. DOI: 10.3390/cells8050496.

28.Siolas D, Hannon GJ. Patient-derived tumor xenografts: transforming clinical samples into mouse models[J]. Cancer Res, 2013, 73(17): 5315-5319. DOI: 10.1158/0008-5472.can-13-1069.

29.Beshiri ML, Tice CM, Tran C, et al. A PDX/Organoid biobank of advanced prostate cancers captures genomic and phenotypic heterogeneity for disease modeling and therapeutic screening[J]. Clin Cancer Res, 2018, 24(17): 4332-4345. DOI: 10.1158/1078-0432.ccr-18-0409.

30.Saeed K, Rahkama V, Eldfors S, et al. Comprehensive drug testing of patient-derived condi-tionally reprogrammed cells from castration-resistant prostate cancer[J]. Eur Urol, 2017, 71(3): 319-327. DOI: 10.1016/j.eururo.2016.04. 019.

31.Ci X, Hao J, Dong X, et al. Conditionally reprogrammed cells from patient-derived xenograft to model neu-roendocrine prostate cancer development[J]. Cells, 2020, 9(6): 1398-1412. DOI: 10.3390/cells9061398.

32.Hoehn W, Schroeder FH, Reimann JF, et al. Human prostatic adenocarcinoma: some charac-teristics of a serially transplantable line in nude mice (PC 82)[J]. The Prostate, 1980, 1(1): 95-104. DOI: 10.1002/pros.2990010113.

33.Nguyen HM, Vessella RL, Morrissey C, et al. LuCaP prostate cancer patient-derived xeno-grafts reflect the molecular heterogeneity of advanced disease and serve as models for evaluating cancer therapeutics[J]. Prostate, 2017, 77(6): 654-671. DOI: 10.1002/pros.23313.

34.Lin D, Bayani J, Wang Y, et al. Development of metastatic and non-metastatic tumor lines from a patient's prostate cancer specimen-identification of a small subpopulation with met-astatic potential in the primary tumor[J]. Prostate, 2010, 70(15): 1636-1644. DOI: 10.1002/pros. 21199.

35.Corey E, Quinn JE, Emond MJ, et al. Inhibition of androgen-independent growth of prostate cancer xenografts by 17beta-estradiol[J]. Clin Cancer Res, 2002, 8(4): 1003-1007. DOI: 10.1093/carcin/23.4.669.

36.Zhang W, van Weerden WM, de Ridder CM, et al. Ex vivo treatment of prostate tumor tissue recapitulates in vivo therapy response[J]. The Prostate, 2019, 79(4): 390-402.DOI: 10.1002/pros.23745.

37.Vidal SJ, Rodriguez-Bravo V, Quinn SA, et al. A targetable GATA2-IGF2 axis confers aggres-siveness in lethal prostate cancer[J]. Cancer cell, 2015, 27(2): 223-239. DOI: 10.1016/j.ccell.2014.11.013.

38.Mo F, Lin D, Takhar M, et al. Stromal gene expression is predictive for metastatic primary prostate cancer[J].  Eur Urol, 2018, 73(4): 524-532. DOI: 10.1016/j.eururo. 2017.02.038.

39.True LD, Buhler K, Quinn J, et al. A neuroendocrine/small cell prostate carcinoma xeno-graft-LuCaP 49[J]. Am J Pathol, 2002, 161(2): 705-715. DOI: 10.1016/s0002-9440(10)64226-5.

40.Lin D, Dong X, Wang K, et al. Identification of DEK as a potential therapeutic target for neuroendocrine prostate cancer[J]. Oncotarget, 2015, 6(3): 1806-1820. DOI: 10.18632/oncotarget.2809.

41.Tung WL, Wang Y, Gout PW, et al. Use of irinotecan for treatment of small cell carcinoma of the prostate[J]. The Prostate, 2011, 71(7): 675-681. DOI: 10.1002/pros.21283.

42.Wang Y, Xue H, Cutz JC, et al. An orthotopic metastatic prostate cancer model in SCID mice via grafting of a transplantable human prostate tumor line[J]. Lab Invest, 2005, 85(11): 1392-1404. DOI: 10.1038/labinvest. 3700335.

43.Lin D, Watahiki A, Bayani J, et al. ASAP1, a gene at 8q24, is associated with prostate cancer metastasis[J]. Cancer Res, 2008, 68(11): 4352-4359. DOI: 10.1158/0008-5472.can-07-5237.

44.Salem AF, Gambini L, Billet S, et al. Prostate cancer metastases are strongly inhibited by ag-onistic epha2 ligands in an orthotopic mouse model[J]. Cancers, 2020, 12(10): 2854-2866. DOI: 10.3390/cancers12102854.

45.Craft N, Chhor C, Tran C, et al. Evidence for clonal outgrowth of androgen-independent prostate cancer cells from androgen-dependent tumors through a two-step process[J]. Cancer Res, 1999, 59(19): 5030-5036.

46.Karkampouna S, La Manna F, Benjak A, et al. Patient-derived xenografts and organoids model therapy response in prostate cancer[J]. Nat Commun, 2021, 12(1): 1117. DOI: 10.1038/s41467-021-21300-6.

47.Karkampouna S, De Filippo MR, Ng CK, et al. Stroma transcriptomic and proteomic profile of prostate cancer metastasis xenograft models reveals prognostic value of stroma signa-tures[J]. Cancers, 2020, 12(12): 3786-3815.DOI: 10.3390/cancers12123786.

48.Tzelepi V, Zhang J, Lu JF, et al. Modeling a lethal prostate cancer variant with small-cell car-cinoma features [J]. Clin Cancer Res, 2012, 18(3): 666-677. DOI: 10.1158/1078-0432.ccr-11-1867.

49.Lam HM, McMullin R, Nguyen HM, et al. Characterization of an abiraterone ultraresponsive phenotype in castration-resistant prostate cancer patient-derived xenografts [J]. Clin Cancer Res, 2017, 23(9): 2301-2312. DOI: 10.1158/1078-0432.ccr-16-2054.

50.Jin L, Garcia J, Chan E, et al. Therapeutic targeting of the CBP/p300 bromodomain blocks the growth of castration-resistant prostate cancer[J]. Cancer Res, 2017, 77(20): 5564-5575. DOI: 10.1158/0008-5472.can-17-0314.

51.Lasko LM, Jakob CG, Edalji RP, et al. Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours[J]. Nature, 2017, 550(7674): 128-132.DOI: 10.1038/nature24028.

52.Suominen MI, Fagerlund KM, Rissanen JP, et al. Radium-223 inhibits osseous prostate cancer growth by dual targeting of cancer cells and bone microenvironment in mouse models [J]. Clin Cancer Res, 2017, 23(15): 4335-4346. DOI: 10.1158/1078-0432.ccr-16-2955.

53.Wang Y, Jiang X, Feng F, et al. Degradation of proteins by PROTACs and other strategies[J]. Acta Pharm Sin B, 2020, 10(2): 207-238. DOI: 10.1016/j.apsb.2019.08.001.

54.Bishop JL, Thaper D, Vahid S, et al. The master neural transcription factor BRN2 is an an-drogen receptor-suppressed driver of neuroendocrine differentiation in prostate cancer[J]. Cancer Discov, 2017, 7(1): 54-71. DOI: 10.1158/

55.Li Y, Donmez N, Sahinalp C, et al. SRRM4 drives neuroendocrine transdifferentiation of prostate adenocarcinoma under androgen receptor pathway inhibition[J]. Eur Urol, 2017, 71(1): 68-78. DOI: 10.1016/j.eururo.2016.04.028.

56.Ci X, Hao J, Dong X, et al. Heterochromatin protein 1α mediates development and aggres-siveness of neuroendocrine prostate cancer[J]. Cancer Res, 2018, 78(10): 2691-2704. DOI: 10.1158/0008-5472.can-17-3677.

57.Guo H, Ci X, Ahmed M, et al. ONECUT2 is a driver of neuroendocrine prostate cancer[J]. Nat Commun, 2019, 10(1): 278-291. DOI: 10.1038/s41467-018-08133-6.

58.Zhang X, Coleman IM, Brown LG, et al. SRRM4 expression and the loss of REST activity may promote the emergence of the neuroendocrine phenotype in castration-resistant prostate cancer[J]. Clin Cancer Res, 2015, 21(20): 4698-4708. DOI: 10.1158/1078-0432.ccr-15-0157.

59.Bakht MK, Derecichei I, Li Y, et al. Neuroendocrine differentiation of prostate cancer leads to PSMA suppression[J]. Endocr Relat Cancer, 2018, 26(2): 131-146. DOI: 10.1530/erc-18-0226.

60.Flores-Morales A, Bergmann TB, Lavallee C, et al. Proteogenomic characterization of patient-derived xeno-grafts highlights the role of REST in neuroendocrine differentiation of castration-resistant prostate cancer[J]. Clin Cancer Res, 2019, 25(2): 595-608. DOI: 10.1158/1078-0432.ccr-18-0729.

61.Meulenbeld HJ, Bleuse JP, Vinci EM, et al. Randomized phase II study of danusertib in pa-tients with metastatic castration-resistant prostate cancer after docetaxel failure[J]. BJU Int, 2013, 111(1): 44-52. DOI: 10.1111/j.1464-410X.2012.11404.x.

62.Beltran H, Rickman DS, Park K, et al. Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets[J]. Cancer discov, 2011, 1(6): 487-495. DOI: 10.1158/

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