An Overview of the Bench to Bedside Models of Breast Cancer in the Era of Cancer Immunotherapy
Main Article Content
Abstract
One of the barriers to novel treatment developments within breast cancer is the ability to prove efficacy in the preclinical setting before moving on to clinical trials. Preclinical models range from single cell monolayers to more sophisticated humanised PDXs systems each with their set of advantages and limitations. Modelling the immune environment in cold tumours, such as breast cancer can also be challenging as are currently no clearly defined markers that can stratify patients based on treatment response. Immune checkpoints receptors such as PD-L1 may not show predictive outcomes in this tumour type. Furthermore, the heterogeneity of breast cancer may be difficult to recapitulate at the bench side. In this review, we provide an overview of the available in vitro, in vivo and ex vivo models of breast cancer with consideration of how these may extrapolated to the investigation of the role of the immune system and immunotherapy developments in breast cancer.
Article Details
How to Cite
KWAN, Amy et al.
An Overview of the Bench to Bedside Models of Breast Cancer in the Era of Cancer Immunotherapy.
Medical Research Archives, [S.l.], v. 12, n. 6, june 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5514>. Date accessed: 23 nov. 2024.
doi: https://doi.org/10.18103/mra.v12i6.5514.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Deluche E, Antoine A, Bachelot T, et al. Contemporary outcomes of metastatic breast cancer among 22,000 women from the multicentre ESME cohort 2008-2016. Eur J Cancer. 2020;129:60-70. Doi:10.1016/j.ejca.2020.01.016
2. Meegdes M, Geurts SME, Erdkamp FLG, et al. Real-world time trends in overall survival, treatments and patient characteristics in HR+/HER2- metastatic breast cancer: an observational study of the SONABRE Registry. The Lancet regional health Europe. 2023;26:100573. Doi:10.1016/j.lanepe.2022.100573
3. Welt A, Bogner S, Arendt M, et al. Improved survival in metastatic breast cancer: results from a 20-year study involving 1033 women treated at a single comprehensive cancer center. J Cancer Res Clin Oncol. 2020;146(6):1559-1566. Doi:10.1007/s00432-020-03184-z
4. Gottardis MM, Robinson SP, Jordan VC. Estradiol-stimulated growth of MCF-7 tumors implanted in athymic mice: A model to study the tumoristatic action of tamoxifen. J Steroid Biochem. 1988;30(1-6):311-314. Doi:10.1016/0022-4731(88)90113-6
5. Foulkes WD, Smith IE, Reis-Filho JS. Triple-Negative Breast Cancer. New England Journal of Medicine. 2010;363(20):1938-1948. Doi:10.1056/NEJMra1001389
6. Weigelt B, Mackay A, A’hern R, et al. Breast cancer molecular profiling with single sample predictors: a retrospective analysis. Lancet Oncol. 2010;11(4):339-349. Doi:10.1016/S1470-2045(10)70008-5
7. Betriu N, Andreeva A, Semino CE. Erlotinib Promotes Ligand-Induced EGFR Degradation in 3D but Not 2D Cultures of Pancreatic Ductal Adenocarcinoma Cells. Cancers (Basel). 2021;13(18):4504. Doi:10.3390/cancers13184504
8. Hollern DP, Andrechek ER. A genomic analysis of mouse models of breast cancer reveals molecular features ofmouse models and relationships to human breast cancer. Breast Cancer Research. 2014;16(3):R59. Doi:10.1186/bcr3672
9. Contardi E, Palmisano GL, Tazzari PL, et al. CTLA-4 is constitutively expressed on tumor cells and can trigger apoptosis upon ligand interaction. Int J Cancer. 2005;117(4):538-550. Doi:10.1002/ijc.21155
10. Zhou S, Zhu M, Meng F, et al. Evaluation of PD-1 blockade using a multicellular tumor spheroid model. Am J Transl Res. 2019;11(12):7471-7478.
11. McKenna MK, Rosewell-Shaw A, Suzuki M. Modeling the Efficacy of Oncolytic Adenoviruses In Vitro and In Vivo: Current and Future Perspectives. Cancers (Basel). 2020;12(3):619. Doi:10.3390/cancers12030619
12. Aung A, Kumar V, Theprungsirikul J, Davey SK, Varghese S. An Engineered Tumor-on-a-Chip Device with Breast Cancer–Immune Cell Interactions for Assessing T-cell Recruitment. Cancer Res. 2020;80(2):263-275. Doi:10.1158/0008-5472.CAN-19-0342
13. Koh EK, Lee HR, Son WC, et al. Combinatorial immunotherapy with gemcitabine and ex vivo-expanded NK cells induces anti-tumor effects in pancreatic cancer. Sci Rep. 2023;13(1):7656. Doi:10.1038/s41598-023-34827-z
14. van Elsas A, Hurwitz AA, Allison JP. Combination Immunotherapy of B16 Melanoma Using Anti–Cytotoxic T Lymphocyte–Associated Antigen 4 (Ctla-4) and Granulocyte/Macrophage Colony-Stimulating Factor (Gm-Csf)-Producing Vaccines Induces Rejection of Subcutaneous and Metastatic Tumors Accompanied by Autoimmune Depigmentation. J Exp Med. 1999;190(3):355-366. Doi:10.1084/jem.190.3.355
15. Katano I, Hanazawa A, Otsuka I, et al. Development of a novel humanized mouse model for improved evaluation of in vivo anti-cancer effects of anti-PD-1 antibody. Sci Rep. 2021;11(1):21087. Doi:10.1038/s41598-021-00641-8
16. Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proceedings of the National Academy of Sciences. 2002;99(19):12293-12297. Doi:10.1073/pnas.192461099
17. Tan SQ, Lee Y, Lee FYX, et al. Ex vivo co-culture models for immunotherapy with patient-derived tumor infiltrating lymphocytes, peripheral blood mononuclear cells and autologous patient colorectal cancer (CRC) cell lines. Journal of Clinical Oncology. 2018;36(15_suppl):e15531-e15531. Doi:10.1200/JCO.2018.36.15_suppl.e15531
18. Votanopoulos KI, Forsythe S, Sivakumar H, et al. Model of Patient-Specific Immune-Enhanced Organoids for Immunotherapy Screening: Feasibility Study. Ann Surg Oncol. 2020;27(6):1956-1967. Doi:10.1245/s10434-019-08143-8
19. Rosato RR, Dávila-González D, Choi DS, et al. Evaluation of anti-PD-1-based therapy against triple-negative breast cancer patient-derived xenograft tumors engrafted in humanized mouse models. Breast Cancer Research. 2018;20(1):108. Doi:10.1186/s13058-018-1037-4
20. Shiravand Y, Khodadadi F, Kashani SMA, et al. Immune Checkpoint Inhibitors in Cancer Therapy. Current Oncology. 2022;29(5):3044-3060. Doi:10.3390/curroncol29050247
21. Cortes J, Rugo HS, Cescon DW, et al. Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. New England Journal of Medicine. 2022;387(3):217-226. Doi:10.1056/nejmoa2202809
22. Schmid P, Cortes J, Dent R, et al. Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. New England Journal of Medicine. 2022;386(6):556-567. Doi:10.1056/nejmoa2112651
23. Schmid P, Adams S, Rugo HS, et al. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. New England Journal of Medicine. 2018;379(22):2108-2121. Doi:10.1056/NEJMoa1809615
24. Miles D, Gligorov J, André F, et al. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Annals of Oncology. 2021;32(8):994-1004. Doi:10.1016/j.annonc.2021.05.801
25. Lehmann BD, Abramson VG, Dees EC, et al. Atezolizumab in Combination With Carboplatin and Survival Outcomes in Patients With Metastatic Triple-Negative Breast Cancer. JAMA Oncol. 2024;10(2):193. Doi:10.1001/jamaoncol.2023.5424
26. Yap TA, Bardia A, Dvorkin M, et al. Avelumab Plus Talazoparib in Patients With Advanced Solid Tumors. JAMA Oncol. 2023;9(1):40. Doi:10.1001/jamaoncol.2022.5228
27. Dirix LY, Takacs I, Jerusalem G, et al. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study. Breast Cancer Res Treat. 2018;167(3):671-686. Doi:10.1007/s10549-017-4537-5
28. Mayer EL, Ren Y, Wagle N, et al. PACE: A Randomized Phase II Study of Fulvestrant, Palbociclib, and Avelumab After Progression on Cyclin-Dependent Kinase 4/6 Inhibitor and Aromatase Inhibitor for Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor–Negative Metastatic Breast Cancer. Journal of Clinical Oncology. Published online March 21, 2024. Doi:10.1200/JCO.23.01940
29. Zacharakis N, Huq LM, Seitter SJ, et al. Breast Cancers Are Immunogenic: Immunologic Analyses and a Phase II Pilot Clinical Trial Using Mutation-Reactive Autologous Lymphocytes. Journal of Clinical Oncology. 2022;40(16):1741-1754. Doi:10.1200/JCO.21.02170
30. Clark AS, Zhao F, Klein P, et al. BRACELET-1 (PrE0113): Inducing an inflammatory phenotype in metastatic HR+/HER2- breast cancer with the oncolytic reovirus pelareorep in combination with paclitaxel and avelumab. Journal of Clinical Oncology. 2023;41(16_suppl):1012-1012. Doi:10.1200/JCO.2023.41.16_suppl.1012
31. Kai M, Marx AN, Liu DD, et al. A phase II study of talimogene laherparepvec for patients with inoperable locoregional recurrence of breast cancer. Sci Rep. 2021;11(1):22242. Doi:10.1038/s41598-021-01473-2
32. Cousin S, Toulmonde M, Kind M, et al. Phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced breast cancer. Exp Hematol Oncol. 2022;11(1):104. Doi:10.1186/s40164-022-00338-2
33. Kwan A, Winder N, Atkinson E, et al. Macrophages Mediate the Antitumor Effects of the Oncolytic Virus HSV1716 in Mammary Tumors. Mol Cancer Ther. 2021;20(3):589-601. Doi:10.1158/1535-7163.MCT-20-0748
34. Bourgeois-Daigneault MC, Roy DG, Aitken AS, et al. Neoadjuvant oncolytic virotherapy before surgery sensitizes triple-negative breast cancer to immune checkpoint therapy. Sci Transl Med. 2018;10(422). Doi:10.1126/scitranslmed.aao1641
35. Kapałczyńska M, Kolenda T, Przybyła W, et al. 2D and 3D cell cultures – a comparison of different types of cancer cell cultures. Archives of Medical Science. Published online 2016. Doi:10.5114/aoms.2016.63743
36. Witt BL, Tollefsbol TO. Molecular, Cellular, and Technical Aspects of Breast Cancer Cell Lines as a Foundational Tool in Cancer Research. Life. 2023;13(12):2311. Doi:10.3390/life13122311
37. Dai X, Cheng H, Bai Z, Li J. Breast Cancer Cell Line Classification and Its Relevance with Breast Tumor Subtyping. J Cancer. 2017;8(16):3131-3141. Doi:10.7150/jca.18457
38. Holliday DL, Speirs V. Choosing the right cell line for breast cancer research. Breast Cancer Research. 2011;13(4):215. Doi:10.1186/bcr2889
39. Lamberti MJ, Nigro A, Mentucci FM, Rumie Vittar NB, Casolaro V, Dal Col J. Dendritic Cells and Immunogenic Cancer Cell Death: A Combination for Improving Antitumor Immunity. Pharmaceutics. 2020;12(3):256. Doi:10.3390/pharmaceutics12030256
40. Fucikova J, Kepp O, Kasikova L, et al. Detection of immunogenic cell death and its relevance for cancer therapy. Cell Death Dis. 2020;11(11):1013. Doi:10.1038/s41419-020-03221-2
41. Krysko D V., Demuynck R, Efimova I, Naessens F, Krysko O, Catanzaro E. In Vitro Veritas: From 2D Cultures to Organ-on-a-Chip Models to Study Immunogenic Cell Death in the Tumor Microenvironment. Cells. 2022;11(22):3705. Doi:10.3390/cells11223705
42. Ma J, Ramachandran M, Jin C, et al. Characterization of virus-mediated immunogenic cancer cell death and the consequences for oncolytic virus-based immunotherapy of cancer. Cell Death Dis. 2020;11(1):48. Doi:10.1038/s41419-020-2236-3
43. Valančiūtė A, Mathieson L, O’Connor RA, et al. Phototherapeutic Induction of Immunogenic Cell Death and CD8+ T Cell-Granzyme B Mediated Cytolysis in Human Lung Cancer Cells and Organoids. Cancers (Basel). 2022;14(17): 4119. Doi:10.3390/cancers14174119
44. Langhans SA. Three-Dimensional in Vitro Cell Culture Models in Drug Discovery and Drug Repositioning. Front Pharmacol. 2018;9. Doi:10.3389/fphar.2018.00006
45. Arrigoni C, Bersini S, Gilardi M, Moretti M. In Vitro Co-Culture Models of Breast Cancer Metastatic Progression towards Bone. Int J Mol Sci. 2016;17(9):1405. Doi:10.3390/ijms17091405
46. Saraiva DP, Matias AT, Braga S, Jacinto A, Cabral MG. Establishment of a 3D Co-culture With MDA-MB-231 Breast Cancer Cell Line and Patient-Derived Immune Cells for Application in the Development of Immunotherapies. Front Oncol. 2020;10. Doi:10.3389/fonc.2020.01543
47. Tevis KM, Cecchi RJ, Colson YL, Grinstaff MW. Mimicking the tumor microenvironment to regulate macrophage phenotype and assessing chemotherapeutic efficacy in embedded cancer cell/macrophage spheroid models. Acta Biomater. 2017;50:271-279. Doi:10.1016/j.actbio.2016.12.037
48. Cavo M, Caria M, Pulsoni I, Beltrame F, Fato M, Scaglione S. A new cell-laden 3D Alginate-Matrigel hydrogel resembles human breast cancer cell malignant morphology, spread and invasion capability observed “in vivo.” Sci Rep. 2018;8(1):5333. Doi:10.1038/s41598-018-23250-4
49. Horder H, Guaza Lasheras M, Grummel N, et al. Bioprinting and Differentiation of Adipose-Derived Stromal Cell Spheroids for a 3D Breast Cancer-Adipose Tissue Model. Cells. 2021;10(4):803. Doi:10.3390/cells10040803
50. Blyth RRR, Birts CN, Beers SA. The role of three-dimensional in vitro models in modelling the inflammatory microenvironment associated with obesity in breast cancer. Breast Cancer Research. 2023;25(1):104. Doi:10.1186/s13058-023-01700-w
51. Verhulsel M, Vignes M, Descroix S, Malaquin L, Vignjevic DM, Viovy JL. A review of microfabrication and hydrogel engineering for micro-organs on chips. Biomaterials. 2014;35(6):1816-1832. Doi:10.1016/j.biomaterials.2013.11.021
52. Zervantonakis IK, Hughes-Alford SK, Charest JL, Condeelis JS, Gertler FB, Kamm RD. Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function. Proceedings of the National Academy of Sciences. 2012;109(34):13515-13520. Doi:10.1073/pnas.1210182109
53. Boussommier-Calleja A, Atiyas Y, Haase K, Headley M, Lewis C, Kamm RD. The effects of monocytes on tumor cell extravasation in a 3D vascularized microfluidic model. Biomaterials. 2019;198:180-193. Doi:10.1016/j.biomaterials.2018.03.005
54. Bai J, Adriani G, Dang TM, et al. Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions. Oncotarget. 2015;6(28):25295-25307. Doi:10.18632/oncotarget.4716
55. Bischel LL, Young EWK, Mader BR, Beebe DJ. Tubeless microfluidic angiogenesis assay with three-dimensional endothelial-lined microvessels. Biomaterials. 2013;34(5):1471-1477. Doi:10.1016/j.biomaterials.2012.11.005
56. Whisler JA, Chen MB, Kamm RD. Control of Perfusable Microvascular Network Morphology Using a Multiculture Microfluidic System. Tissue Eng Part C Methods. 2014;20(7):543-552. Doi:10.1089/ten.tec.2013.0370
57. Shin Y, Han S, Jeon JS, et al. Microfluidic assay for simultaneous culture of multiple cell types on surfaces or within hydrogels. Nat Protoc. 2012;7(7):1247-1259. Doi:10.1038/nprot.2012.051
58. Lee SW, Lee KJ, Jeong SY, Joo CH, Lee H, Jeong GS. Evaluation of Bystander Infection of Oncolytic Virus using a Medium Flow Integrated 3D In Vitro Microphysiological System. Adv Biosyst. 2020;4(2). Doi:10.1002/adbi.201900143
59. Bai J, Adriani G, Dang TM, et al. Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions. Oncotarget. 2015;6(28):25295-25307. Doi:10.18632/oncotarget.4716
60. Boussommier-Calleja A, Atiyas Y, Haase K, Headley M, Lewis C, Kamm RD. The effects of monocytes on tumor cell extravasation in a 3D vascularized microfluidic model. Biomaterials. 2019;198:180-193. Doi:10.1016/j.biomaterials.2018.03.005
61. Jeon JS, Bersini S, Gilardi M, et al. Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation. Proceedings of the National Academy of Sciences. 2015;112(1):214-219. Doi:10.1073/pnas.1417115112
62. Fantozzi A, Christofori G. Mouse models of breast cancer metastasis. Breast Cancer Research. 2006;8(4):212. Doi:10.1186/bcr1530
63. Doyle A, McGarry MP, Lee NA, Lee JJ. The construction of transgenic and gene knockout/knockin mouse models of human disease. Transgenic Res. 2012;21(2):327-349. Doi:10.1007/s11248-011-9537-3
64. Yarchoan M, Johnson BA, Lutz ER, Laheru DA, Jaffee EM. Targeting neoantigens to augment antitumour immunity. Nat Rev Cancer. 2017;17(4):209-222. Doi:10.1038/nrc.2016.154
65. Becher OJ, Holland EC. Genetically Engineered Models Have Advantages over Xenografts for Preclinical Studies. Cancer Res. 2006;66(7):3355-3359. Doi:10.1158/0008-5472.CAN-05-3827
66. McCarthy A, Savage K, Gabriel A, Naceur C, Reis‐Filho J, Ashworth A. A mouse model of basal‐like breast carcinoma with metaplastic elements. J Pathol. 2007;211(4):389-398. Doi:10.1002/path.2124
67. Graveel CR, DeGroot JD, Su Y, et al. Met induces diverse mammary carcinomas in mice and is associated with human basal breast cancer. Proceedings of the National Academy of Sciences. 2009;106(31):12909-12914. Doi:10.1073/pnas.0810403106
68. Stewart TA, Pattengale PK, Leder P. Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTV/myc fusion genes. Cell. 1984;38(3):627-637. Doi:10.1016/0092-8674(84)90257-5
69. Stepanova L, Finegold M, DeMayo F, Schmidt E V., Harper JW. The Oncoprotein Kinase Chaperone CDC37 Functions as an Oncogene in Mice and Collaborates with Both c- myc and Cyclin D1 in Transformation of Multiple Tissues. Mol Cell Biol. 2000;20(12):4462-4473. Doi:10.1128/MCB.20.12.4462-4473.2000
70. Pénzváltó Z, Chen JQ, Tepper CG, et al. A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials. J Mammary Gland Biol Neoplasia. 2019;24(2):149-162. Doi:10.1007/s10911-019-09425-3
71. Sinn E, Muller W, Pattengale P, Tepler I, Wallace R, Leder P. Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: Synergistic action of oncogenes in vivo. Cell. 1987;49(4):465-475. Doi:10.1016/0092-8674(87)90449-1
72. Jones RA, Campbell CI, Gunther EJ, et al. Transgenic overexpression of IGF-IR disrupts mammary ductal morphogenesis and induces tumor formation. Oncogene. 2007;26(11):1636-1644. Doi:10.1038/sj.onc.1209955
73. Adams JR, Xu K, Liu JC, et al. Cooperation between Pik3ca and p53 Mutations in Mouse Mammary Tumor Formation. Cancer Res. 2011;71(7):2706-2717. Doi:10.1158/0008-5472.CAN-10-0738
74. Li G, Robinson GW, Lesche R, et al. Conditional loss of PTEN leads to precocious development and neoplasia in the mammary gland. Development. 2002;129(17):4159-4170. Doi:10.1242/dev.129.17.4159
75. Attalla S, Taifour T, Bui T, Muller W. Insights from transgenic mouse models of PyMT-induced breast cancer: recapitulating human breast cancer progression in vivo. Oncogene. 2021;40(3):475-491. Doi:10.1038/s41388-020-01560-0
76. Jiang Z, Deng T, Jones R, et al. Rb deletion in mouse mammary progenitors induces luminal-B or basal-like/EMT tumor subtypes depending on p53 status. Journal of Clinical Investigation. 2010;120(9):3296-3309. Doi:10.1172/JCI41490
77. Green JE, Shibata MA, Yoshidome K, et al. The C3(1)/SV40 T-antigen transgenic mouse model of mammary cancer: ductal epithelial cell targeting with multistage progression to carcinoma. Oncogene. 2000;19(8):1020-1027. Doi:10.1038/sj.onc.1203280
78. Serra R, Crowley MR. Mouse models of transforming growth factor β impact in breast development and cancer. Endocr Relat Cancer. 2005;12(4):749-760. Doi:10.1677/erc.1.00936
79. Pfefferle AD, Darr DB, Calhoun BC, Mott KR, Rosen JM, Perou CM. The MMTV-Wnt1 murine model produces two phenotypically distinct subtypes of mammary tumors with unique therapeutic responses to an EGFR inhibitor. Dis Model Mech. Published online January 1, 2019. Doi:10.1242/dmm.037192
80. Tilli MT, Frech MS, Steed ME, et al. Introduction of Estrogen Receptor-α into the tTA/TAg Conditional Mouse Model Precipitates the Development of Estrogen-Responsive Mammary Adenocarcinoma. Am J Pathol. 2003;163(5):1713-1719. Doi:10.1016/S0002-9440(10)63529-8
81. Hollern DP, Contreras CM, Dance-Barnes S, et al. A mouse model featuring tissue-specific deletion of p53 and Brca1 gives rise to mammary tumors with genomic and transcriptomic similarities to human basal-like breast cancer. Breast Cancer Res Treat. 2019;174(1):143-155. Doi:10.1007/s10549-018-5061-y
82. Doha ZO, Wang X, Calistri NL, et al. MYC Deregulation and PTEN Loss Model Tumor and Stromal Heterogeneity of Aggressive Triple-Negative Breast Cancer. Nat Commun. 2023;14(1):5665. Doi:10.1038/s41467-023-40841-6
83. Jones LM, Broz ML, Ranger JJ, et al. STAT3 Establishes an Immunosuppressive Microenvironment during the Early Stages of Breast Carcinogenesis to Promote Tumor Growth and Metastasis. Cancer Res. 2016;76(6):1416-1428. Doi:10.1158/0008-5472.CAN-15-2770
84. Hollern DP, Xu N, Thennavan A, et al. B Cells and T Follicular Helper Cells Mediate Response to Checkpoint Inhibitors in High Mutation Burden Mouse Models of Breast Cancer. Cell. 2019;179(5):1191-1206.e21. Doi:10.1016/j.cell.2019.10.028
85. Dobrolecki LE, Airhart SD, Alferez DG, et al. Patient-derived xenograft (PDX) models in basic and translational breast cancer research. Cancer and Metastasis Reviews. 2016;35(4):547-573. Doi:10.1007/s10555-016-9653-x
86. Lefley D, Howard F, Arshad F, et al. Development of clinically relevant in vivo metastasis models using human bone discs and breast cancer patient-derived xenografts. Breast Cancer Res. 2019;21(1):130. Doi:10.1186/s13058-019-1220-2
87. Pettersen S, Øy GF, Egeland EV, et al. Breast cancer patient-derived explant cultures recapitulate in vivo drug responses. Front Oncol. 2023;13. Doi:10.3389/fonc.2023.1040665
88. Choi Y, Lee S, Kim K, Kim SH, Chung YJ, Lee C. Studying cancer immunotherapy using patient-derived xenografts (PDXs) in humanized mice. Exp Mol Med. 2018;50(8):1-9. Doi:10.1038/s12276-018-0115-0
89. Masemann D, Ludwig S, Boergeling Y. Advances in Transgenic Mouse Models to Study Infections by Human Pathogenic Viruses. Int J Mol Sci. 2020;21(23):9289. Doi:10.3390/ijms21239289
90. Morton JJ, Bird G, Keysar SB, et al. XactMice: humanizing mouse bone marrow enables microenvironment reconstitution in a patient-derived xenograft model of head and neck cancer. Oncogene. 2016;35(3):290-300. Doi:10.1038/onc.2015.94
91. Wang M, Yao L, Cheng M, et al. Humanized mice in studying efficacy and mechanisms of PD‐1‐targeted cancer immunotherapy. The FASEB Journal. 2018;32(3):1537-1549. Doi:10.1096/fj.201700740R
92. Zhao Y, Shuen TWH, Toh TB, et al. Development of a new patient-derived xenograft humanised mouse model to study human-specific tumour microenvironment and immunotherapy. Gut. 2018;67(10):1845-1854. Doi:10.1136/gutjnl-2017-315201
93. Morton JJ, Alzofon N, Keysar SB, et al. Studying Immunotherapy Resistance in a Melanoma Autologous Humanized Mouse Xenograft. Molecular Cancer Research. 2021;19(2):346-357. Doi:10.1158/1541-7786.MCR-20-0686
94. Marín-Jiménez JA, Capasso A, Lewis MS, et al. Testing Cancer Immunotherapy in a Human Immune System Mouse Model: Correlating Treatment Responses to Human Chimerism, Therapeutic Variables and Immune Cell Phenotypes. Front Immunol. 2021;12. Doi:10.3389/fimmu.2021.607282
95. Pyo KH, Kim JH, Lee JM, et al. Promising preclinical platform for evaluation of immuno-oncology drugs using Hu-PBL-NSG lung cancer models. Lung Cancer. 2019;127:112-121. Doi:10.1016/j.lungcan.2018.11.035
96. Meraz IM, Majidi M, Meng F, et al. An Improved Patient-Derived Xenograft Humanized Mouse Model for Evaluation of Lung Cancer Immune Responses. Cancer Immunol Res. 2019;7(8):1267-1279. Doi:10.1158/2326-6066.CIR-18-0874
97. Kang Y, Armstrong AJ, Hsu DS. An autologous humanized patient-derived xenograft (PDX) model for evaluation of nivolumab immunotherapy in renal cell cancer: a case report. Stem Cell Investig. 2022;9:8-8. Doi:10.21037/sci-2022-029
98. Rosato RR, Dávila-González D, Choi DS, et al. Evaluation of anti-PD-1-based therapy against triple-negative breast cancer patient-derived xenograft tumors engrafted in humanized mouse models. Breast Cancer Research. 2018;20(1):108. Doi:10.1186/s13058-018-1037-4
99. Liu WN, Fong SY, Tan WWS, et al. Establishment and Characterization of Humanized Mouse NPC-PDX Model for Testing Immunotherapy. Cancers (Basel). 2020;12(4):1025. Doi:10.3390/cancers12041025
100. Rosato RR, Dávila-González D, Choi DS, et al. Evaluation of anti-PD-1-based therapy against triple-negative breast cancer patient-derived xenograft tumors engrafted in humanized mouse models. Breast Cancer Research. 2018;20(1):108. Doi:10.1186/s13058-018-1037-4
101. Loibl S, Poortmans P, Morrow M, Denkert C, Curigliano G. Breast cancer. The Lancet. 2021;397(10286):1750-1769. Doi:10.1016/S0140-6736(20)32381-3
102. Bruss C, Kellner K, Albert V, et al. Immune Checkpoint Profiling in Humanized Breast Cancer Mice Revealed Cell-Specific LAG-3/PD-1/TIM-3 Co-Expression and Elevated PD-1/TIM-3 Secretion. Cancers (Basel). 2023;15(9):2615. Doi:10.3390/cancers15092615
103. Scherer SD, Riggio AI, Haroun F, et al. An immune-humanized patient-derived xenograft model of estrogen-independent, hormone receptor positive metastatic breast cancer. Breast Cancer Research. 2021;23(1):100. Doi:10.1186/s13058-021-01476-x
104. Yu J, Qin B, Moyer AM, et al. Establishing and characterizing patient-derived xenografts using pre-chemotherapy percutaneous biopsy and post-chemotherapy surgical samples from a prospective neoadjuvant breast cancer study. Breast Cancer Research. 2017;19(1):130. Doi:10.1186/s13058-017-0920-8
105. Guillen KP, Fujita M, Butterfield AJ, et al. A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology. Nat Cancer. 2022;3(2):232-250. Doi:10.1038/s43018-022-00337-6
106. Liu Y, Wu W, Cai C, Zhang H, Shen H, Han Y. Patient-derived xenograft models in cancer therapy: technologies and applications. Signal Transduct Target Ther. 2023;8(1):160. Doi:10.1038/s41392-023-01419-2
107. Muraro MG, Muenst S, Mele V, et al. Ex-vivo assessment of drug response on breast cancer primary tissue with preserved microenvironments. Oncoimmunology. Published online May 30, 2017:e1331798. Doi:10.1080/2162402X.2017.1331798
108. Urbaniak A, Piña-Oviedo S, Yuan Y, Huczyński A, Chambers TC. Limitations of an ex vivo breast cancer model for studying the mechanism of action of the anticancer drug paclitaxel. Eur J Pharmacol. 2021;891:173780. Doi:10.1016/j.ejphar.2020.173780
109. Karekla E, Liao WJ, Sharp B, et al. Ex Vivo Explant Cultures of Non–Small Cell Lung Carcinoma Enable Evaluation of Primary Tumor Responses to Anticancer Therapy. Cancer Res. 2017;77(8):2029-2039. Doi:10.1158/0008-5472.CAN-16-1121
110. Yang R, Yu Y. Patient-derived organoids in translational oncology and drug screening. Cancer Lett. 2023;562:216180. Doi:10.1016/j.canlet.2023.216180
111. Sachs N, de Ligt J, Kopper O, et al. A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity. Cell. 2018;172(1-2):373-386.e10. Doi:10.1016/j.cell.2017.11.010
112. Peng D, Gleyzer R, Tai WH, et al. Evaluating the transcriptional fidelity of cancer models. Genome Med. 2021;13(1):73. Doi:10.1186/s13073-021-00888-w
113. Chakrabarti J, Koh V, So JBY, Yong WP, Zavros Y. A Preclinical Human-Derived Autologous Gastric Cancer Organoid/Immune Cell Co-Culture Model to Predict the Efficacy of Targeted Therapies. Journal of Visualized Experiments. 2021;(173). Doi:10.3791/61443
114. Tsai S, McOlash L, Palen K, et al. Development of primary human pancreatic cancer organoids, matched stromal and immune cells and 3D tumor microenvironment models. BMC Cancer. 2018;18(1):335. Doi:10.1186/s12885-018-4238-4
115. Michie J, Beavis PA, Freeman AJ, et al. Antagonism of IAPs Enhances CAR T-cell Efficacy. Cancer Immunol Res. 2019;7(2):183-192. Doi:10.1158/2326-6066.CIR-18-0428
116. Jenkins RW, Aref AR, Lizotte PH, et al. Ex Vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids. Cancer Discov. 2018;8(2):196-215. Doi:10.1158/2159-8290.CD-17-0833
117. Snijder B, Vladimer GI, Krall N, et al. Image-based ex-vivo drug screening for patients with aggressive haematological malignancies: interim results from a single-arm, open-label, pilot study. Lancet Haematol. 2017;4(12):e595-e606. Doi:10.1016/S2352-3026(17)30208-9
118. Williams ST, Wells G, Conroy S, et al. Precision oncology using ex vivo technology: a step towards individualised cancer care? Expert Rev Mol Med. 2022;24:e39. Doi:10.1017/erm.2022.32
119. Ladan MM, Meijer TG, Verkaik NS, et al. Functional Ex Vivo Tissue-Based Chemotherapy Sensitivity Testing for Breast Cancer. Cancers (Basel). 2022;14(5):1252. Doi:10.3390/cancers14051252
120. Ladan MM, Meijer TG, Verkaik NS, et al. Proof-of-concept study linking ex vivo sensitivity testing to neoadjuvant anthracycline-based chemotherapy response in breast cancer patients. NPJ Breast Cancer. 2023;9(1):80. Doi:10.1038/s41523-023-00583-6
121. Jordan VC. 50th anniversary of the first clinical trial with ICI 46,474 (tamoxifen): then what happened? Endocr Relat Cancer. 2021;28(1):R11-R30. Doi:10.1530/ERC-20-0335
122. David Shaywitz. The Startling History Behind Merck’s New Cancer Blockbuster. Forbes Magazine
2. Meegdes M, Geurts SME, Erdkamp FLG, et al. Real-world time trends in overall survival, treatments and patient characteristics in HR+/HER2- metastatic breast cancer: an observational study of the SONABRE Registry. The Lancet regional health Europe. 2023;26:100573. Doi:10.1016/j.lanepe.2022.100573
3. Welt A, Bogner S, Arendt M, et al. Improved survival in metastatic breast cancer: results from a 20-year study involving 1033 women treated at a single comprehensive cancer center. J Cancer Res Clin Oncol. 2020;146(6):1559-1566. Doi:10.1007/s00432-020-03184-z
4. Gottardis MM, Robinson SP, Jordan VC. Estradiol-stimulated growth of MCF-7 tumors implanted in athymic mice: A model to study the tumoristatic action of tamoxifen. J Steroid Biochem. 1988;30(1-6):311-314. Doi:10.1016/0022-4731(88)90113-6
5. Foulkes WD, Smith IE, Reis-Filho JS. Triple-Negative Breast Cancer. New England Journal of Medicine. 2010;363(20):1938-1948. Doi:10.1056/NEJMra1001389
6. Weigelt B, Mackay A, A’hern R, et al. Breast cancer molecular profiling with single sample predictors: a retrospective analysis. Lancet Oncol. 2010;11(4):339-349. Doi:10.1016/S1470-2045(10)70008-5
7. Betriu N, Andreeva A, Semino CE. Erlotinib Promotes Ligand-Induced EGFR Degradation in 3D but Not 2D Cultures of Pancreatic Ductal Adenocarcinoma Cells. Cancers (Basel). 2021;13(18):4504. Doi:10.3390/cancers13184504
8. Hollern DP, Andrechek ER. A genomic analysis of mouse models of breast cancer reveals molecular features ofmouse models and relationships to human breast cancer. Breast Cancer Research. 2014;16(3):R59. Doi:10.1186/bcr3672
9. Contardi E, Palmisano GL, Tazzari PL, et al. CTLA-4 is constitutively expressed on tumor cells and can trigger apoptosis upon ligand interaction. Int J Cancer. 2005;117(4):538-550. Doi:10.1002/ijc.21155
10. Zhou S, Zhu M, Meng F, et al. Evaluation of PD-1 blockade using a multicellular tumor spheroid model. Am J Transl Res. 2019;11(12):7471-7478.
11. McKenna MK, Rosewell-Shaw A, Suzuki M. Modeling the Efficacy of Oncolytic Adenoviruses In Vitro and In Vivo: Current and Future Perspectives. Cancers (Basel). 2020;12(3):619. Doi:10.3390/cancers12030619
12. Aung A, Kumar V, Theprungsirikul J, Davey SK, Varghese S. An Engineered Tumor-on-a-Chip Device with Breast Cancer–Immune Cell Interactions for Assessing T-cell Recruitment. Cancer Res. 2020;80(2):263-275. Doi:10.1158/0008-5472.CAN-19-0342
13. Koh EK, Lee HR, Son WC, et al. Combinatorial immunotherapy with gemcitabine and ex vivo-expanded NK cells induces anti-tumor effects in pancreatic cancer. Sci Rep. 2023;13(1):7656. Doi:10.1038/s41598-023-34827-z
14. van Elsas A, Hurwitz AA, Allison JP. Combination Immunotherapy of B16 Melanoma Using Anti–Cytotoxic T Lymphocyte–Associated Antigen 4 (Ctla-4) and Granulocyte/Macrophage Colony-Stimulating Factor (Gm-Csf)-Producing Vaccines Induces Rejection of Subcutaneous and Metastatic Tumors Accompanied by Autoimmune Depigmentation. J Exp Med. 1999;190(3):355-366. Doi:10.1084/jem.190.3.355
15. Katano I, Hanazawa A, Otsuka I, et al. Development of a novel humanized mouse model for improved evaluation of in vivo anti-cancer effects of anti-PD-1 antibody. Sci Rep. 2021;11(1):21087. Doi:10.1038/s41598-021-00641-8
16. Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proceedings of the National Academy of Sciences. 2002;99(19):12293-12297. Doi:10.1073/pnas.192461099
17. Tan SQ, Lee Y, Lee FYX, et al. Ex vivo co-culture models for immunotherapy with patient-derived tumor infiltrating lymphocytes, peripheral blood mononuclear cells and autologous patient colorectal cancer (CRC) cell lines. Journal of Clinical Oncology. 2018;36(15_suppl):e15531-e15531. Doi:10.1200/JCO.2018.36.15_suppl.e15531
18. Votanopoulos KI, Forsythe S, Sivakumar H, et al. Model of Patient-Specific Immune-Enhanced Organoids for Immunotherapy Screening: Feasibility Study. Ann Surg Oncol. 2020;27(6):1956-1967. Doi:10.1245/s10434-019-08143-8
19. Rosato RR, Dávila-González D, Choi DS, et al. Evaluation of anti-PD-1-based therapy against triple-negative breast cancer patient-derived xenograft tumors engrafted in humanized mouse models. Breast Cancer Research. 2018;20(1):108. Doi:10.1186/s13058-018-1037-4
20. Shiravand Y, Khodadadi F, Kashani SMA, et al. Immune Checkpoint Inhibitors in Cancer Therapy. Current Oncology. 2022;29(5):3044-3060. Doi:10.3390/curroncol29050247
21. Cortes J, Rugo HS, Cescon DW, et al. Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. New England Journal of Medicine. 2022;387(3):217-226. Doi:10.1056/nejmoa2202809
22. Schmid P, Cortes J, Dent R, et al. Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. New England Journal of Medicine. 2022;386(6):556-567. Doi:10.1056/nejmoa2112651
23. Schmid P, Adams S, Rugo HS, et al. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. New England Journal of Medicine. 2018;379(22):2108-2121. Doi:10.1056/NEJMoa1809615
24. Miles D, Gligorov J, André F, et al. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Annals of Oncology. 2021;32(8):994-1004. Doi:10.1016/j.annonc.2021.05.801
25. Lehmann BD, Abramson VG, Dees EC, et al. Atezolizumab in Combination With Carboplatin and Survival Outcomes in Patients With Metastatic Triple-Negative Breast Cancer. JAMA Oncol. 2024;10(2):193. Doi:10.1001/jamaoncol.2023.5424
26. Yap TA, Bardia A, Dvorkin M, et al. Avelumab Plus Talazoparib in Patients With Advanced Solid Tumors. JAMA Oncol. 2023;9(1):40. Doi:10.1001/jamaoncol.2022.5228
27. Dirix LY, Takacs I, Jerusalem G, et al. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study. Breast Cancer Res Treat. 2018;167(3):671-686. Doi:10.1007/s10549-017-4537-5
28. Mayer EL, Ren Y, Wagle N, et al. PACE: A Randomized Phase II Study of Fulvestrant, Palbociclib, and Avelumab After Progression on Cyclin-Dependent Kinase 4/6 Inhibitor and Aromatase Inhibitor for Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor–Negative Metastatic Breast Cancer. Journal of Clinical Oncology. Published online March 21, 2024. Doi:10.1200/JCO.23.01940
29. Zacharakis N, Huq LM, Seitter SJ, et al. Breast Cancers Are Immunogenic: Immunologic Analyses and a Phase II Pilot Clinical Trial Using Mutation-Reactive Autologous Lymphocytes. Journal of Clinical Oncology. 2022;40(16):1741-1754. Doi:10.1200/JCO.21.02170
30. Clark AS, Zhao F, Klein P, et al. BRACELET-1 (PrE0113): Inducing an inflammatory phenotype in metastatic HR+/HER2- breast cancer with the oncolytic reovirus pelareorep in combination with paclitaxel and avelumab. Journal of Clinical Oncology. 2023;41(16_suppl):1012-1012. Doi:10.1200/JCO.2023.41.16_suppl.1012
31. Kai M, Marx AN, Liu DD, et al. A phase II study of talimogene laherparepvec for patients with inoperable locoregional recurrence of breast cancer. Sci Rep. 2021;11(1):22242. Doi:10.1038/s41598-021-01473-2
32. Cousin S, Toulmonde M, Kind M, et al. Phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced breast cancer. Exp Hematol Oncol. 2022;11(1):104. Doi:10.1186/s40164-022-00338-2
33. Kwan A, Winder N, Atkinson E, et al. Macrophages Mediate the Antitumor Effects of the Oncolytic Virus HSV1716 in Mammary Tumors. Mol Cancer Ther. 2021;20(3):589-601. Doi:10.1158/1535-7163.MCT-20-0748
34. Bourgeois-Daigneault MC, Roy DG, Aitken AS, et al. Neoadjuvant oncolytic virotherapy before surgery sensitizes triple-negative breast cancer to immune checkpoint therapy. Sci Transl Med. 2018;10(422). Doi:10.1126/scitranslmed.aao1641
35. Kapałczyńska M, Kolenda T, Przybyła W, et al. 2D and 3D cell cultures – a comparison of different types of cancer cell cultures. Archives of Medical Science. Published online 2016. Doi:10.5114/aoms.2016.63743
36. Witt BL, Tollefsbol TO. Molecular, Cellular, and Technical Aspects of Breast Cancer Cell Lines as a Foundational Tool in Cancer Research. Life. 2023;13(12):2311. Doi:10.3390/life13122311
37. Dai X, Cheng H, Bai Z, Li J. Breast Cancer Cell Line Classification and Its Relevance with Breast Tumor Subtyping. J Cancer. 2017;8(16):3131-3141. Doi:10.7150/jca.18457
38. Holliday DL, Speirs V. Choosing the right cell line for breast cancer research. Breast Cancer Research. 2011;13(4):215. Doi:10.1186/bcr2889
39. Lamberti MJ, Nigro A, Mentucci FM, Rumie Vittar NB, Casolaro V, Dal Col J. Dendritic Cells and Immunogenic Cancer Cell Death: A Combination for Improving Antitumor Immunity. Pharmaceutics. 2020;12(3):256. Doi:10.3390/pharmaceutics12030256
40. Fucikova J, Kepp O, Kasikova L, et al. Detection of immunogenic cell death and its relevance for cancer therapy. Cell Death Dis. 2020;11(11):1013. Doi:10.1038/s41419-020-03221-2
41. Krysko D V., Demuynck R, Efimova I, Naessens F, Krysko O, Catanzaro E. In Vitro Veritas: From 2D Cultures to Organ-on-a-Chip Models to Study Immunogenic Cell Death in the Tumor Microenvironment. Cells. 2022;11(22):3705. Doi:10.3390/cells11223705
42. Ma J, Ramachandran M, Jin C, et al. Characterization of virus-mediated immunogenic cancer cell death and the consequences for oncolytic virus-based immunotherapy of cancer. Cell Death Dis. 2020;11(1):48. Doi:10.1038/s41419-020-2236-3
43. Valančiūtė A, Mathieson L, O’Connor RA, et al. Phototherapeutic Induction of Immunogenic Cell Death and CD8+ T Cell-Granzyme B Mediated Cytolysis in Human Lung Cancer Cells and Organoids. Cancers (Basel). 2022;14(17): 4119. Doi:10.3390/cancers14174119
44. Langhans SA. Three-Dimensional in Vitro Cell Culture Models in Drug Discovery and Drug Repositioning. Front Pharmacol. 2018;9. Doi:10.3389/fphar.2018.00006
45. Arrigoni C, Bersini S, Gilardi M, Moretti M. In Vitro Co-Culture Models of Breast Cancer Metastatic Progression towards Bone. Int J Mol Sci. 2016;17(9):1405. Doi:10.3390/ijms17091405
46. Saraiva DP, Matias AT, Braga S, Jacinto A, Cabral MG. Establishment of a 3D Co-culture With MDA-MB-231 Breast Cancer Cell Line and Patient-Derived Immune Cells for Application in the Development of Immunotherapies. Front Oncol. 2020;10. Doi:10.3389/fonc.2020.01543
47. Tevis KM, Cecchi RJ, Colson YL, Grinstaff MW. Mimicking the tumor microenvironment to regulate macrophage phenotype and assessing chemotherapeutic efficacy in embedded cancer cell/macrophage spheroid models. Acta Biomater. 2017;50:271-279. Doi:10.1016/j.actbio.2016.12.037
48. Cavo M, Caria M, Pulsoni I, Beltrame F, Fato M, Scaglione S. A new cell-laden 3D Alginate-Matrigel hydrogel resembles human breast cancer cell malignant morphology, spread and invasion capability observed “in vivo.” Sci Rep. 2018;8(1):5333. Doi:10.1038/s41598-018-23250-4
49. Horder H, Guaza Lasheras M, Grummel N, et al. Bioprinting and Differentiation of Adipose-Derived Stromal Cell Spheroids for a 3D Breast Cancer-Adipose Tissue Model. Cells. 2021;10(4):803. Doi:10.3390/cells10040803
50. Blyth RRR, Birts CN, Beers SA. The role of three-dimensional in vitro models in modelling the inflammatory microenvironment associated with obesity in breast cancer. Breast Cancer Research. 2023;25(1):104. Doi:10.1186/s13058-023-01700-w
51. Verhulsel M, Vignes M, Descroix S, Malaquin L, Vignjevic DM, Viovy JL. A review of microfabrication and hydrogel engineering for micro-organs on chips. Biomaterials. 2014;35(6):1816-1832. Doi:10.1016/j.biomaterials.2013.11.021
52. Zervantonakis IK, Hughes-Alford SK, Charest JL, Condeelis JS, Gertler FB, Kamm RD. Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function. Proceedings of the National Academy of Sciences. 2012;109(34):13515-13520. Doi:10.1073/pnas.1210182109
53. Boussommier-Calleja A, Atiyas Y, Haase K, Headley M, Lewis C, Kamm RD. The effects of monocytes on tumor cell extravasation in a 3D vascularized microfluidic model. Biomaterials. 2019;198:180-193. Doi:10.1016/j.biomaterials.2018.03.005
54. Bai J, Adriani G, Dang TM, et al. Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions. Oncotarget. 2015;6(28):25295-25307. Doi:10.18632/oncotarget.4716
55. Bischel LL, Young EWK, Mader BR, Beebe DJ. Tubeless microfluidic angiogenesis assay with three-dimensional endothelial-lined microvessels. Biomaterials. 2013;34(5):1471-1477. Doi:10.1016/j.biomaterials.2012.11.005
56. Whisler JA, Chen MB, Kamm RD. Control of Perfusable Microvascular Network Morphology Using a Multiculture Microfluidic System. Tissue Eng Part C Methods. 2014;20(7):543-552. Doi:10.1089/ten.tec.2013.0370
57. Shin Y, Han S, Jeon JS, et al. Microfluidic assay for simultaneous culture of multiple cell types on surfaces or within hydrogels. Nat Protoc. 2012;7(7):1247-1259. Doi:10.1038/nprot.2012.051
58. Lee SW, Lee KJ, Jeong SY, Joo CH, Lee H, Jeong GS. Evaluation of Bystander Infection of Oncolytic Virus using a Medium Flow Integrated 3D In Vitro Microphysiological System. Adv Biosyst. 2020;4(2). Doi:10.1002/adbi.201900143
59. Bai J, Adriani G, Dang TM, et al. Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions. Oncotarget. 2015;6(28):25295-25307. Doi:10.18632/oncotarget.4716
60. Boussommier-Calleja A, Atiyas Y, Haase K, Headley M, Lewis C, Kamm RD. The effects of monocytes on tumor cell extravasation in a 3D vascularized microfluidic model. Biomaterials. 2019;198:180-193. Doi:10.1016/j.biomaterials.2018.03.005
61. Jeon JS, Bersini S, Gilardi M, et al. Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation. Proceedings of the National Academy of Sciences. 2015;112(1):214-219. Doi:10.1073/pnas.1417115112
62. Fantozzi A, Christofori G. Mouse models of breast cancer metastasis. Breast Cancer Research. 2006;8(4):212. Doi:10.1186/bcr1530
63. Doyle A, McGarry MP, Lee NA, Lee JJ. The construction of transgenic and gene knockout/knockin mouse models of human disease. Transgenic Res. 2012;21(2):327-349. Doi:10.1007/s11248-011-9537-3
64. Yarchoan M, Johnson BA, Lutz ER, Laheru DA, Jaffee EM. Targeting neoantigens to augment antitumour immunity. Nat Rev Cancer. 2017;17(4):209-222. Doi:10.1038/nrc.2016.154
65. Becher OJ, Holland EC. Genetically Engineered Models Have Advantages over Xenografts for Preclinical Studies. Cancer Res. 2006;66(7):3355-3359. Doi:10.1158/0008-5472.CAN-05-3827
66. McCarthy A, Savage K, Gabriel A, Naceur C, Reis‐Filho J, Ashworth A. A mouse model of basal‐like breast carcinoma with metaplastic elements. J Pathol. 2007;211(4):389-398. Doi:10.1002/path.2124
67. Graveel CR, DeGroot JD, Su Y, et al. Met induces diverse mammary carcinomas in mice and is associated with human basal breast cancer. Proceedings of the National Academy of Sciences. 2009;106(31):12909-12914. Doi:10.1073/pnas.0810403106
68. Stewart TA, Pattengale PK, Leder P. Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTV/myc fusion genes. Cell. 1984;38(3):627-637. Doi:10.1016/0092-8674(84)90257-5
69. Stepanova L, Finegold M, DeMayo F, Schmidt E V., Harper JW. The Oncoprotein Kinase Chaperone CDC37 Functions as an Oncogene in Mice and Collaborates with Both c- myc and Cyclin D1 in Transformation of Multiple Tissues. Mol Cell Biol. 2000;20(12):4462-4473. Doi:10.1128/MCB.20.12.4462-4473.2000
70. Pénzváltó Z, Chen JQ, Tepper CG, et al. A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials. J Mammary Gland Biol Neoplasia. 2019;24(2):149-162. Doi:10.1007/s10911-019-09425-3
71. Sinn E, Muller W, Pattengale P, Tepler I, Wallace R, Leder P. Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: Synergistic action of oncogenes in vivo. Cell. 1987;49(4):465-475. Doi:10.1016/0092-8674(87)90449-1
72. Jones RA, Campbell CI, Gunther EJ, et al. Transgenic overexpression of IGF-IR disrupts mammary ductal morphogenesis and induces tumor formation. Oncogene. 2007;26(11):1636-1644. Doi:10.1038/sj.onc.1209955
73. Adams JR, Xu K, Liu JC, et al. Cooperation between Pik3ca and p53 Mutations in Mouse Mammary Tumor Formation. Cancer Res. 2011;71(7):2706-2717. Doi:10.1158/0008-5472.CAN-10-0738
74. Li G, Robinson GW, Lesche R, et al. Conditional loss of PTEN leads to precocious development and neoplasia in the mammary gland. Development. 2002;129(17):4159-4170. Doi:10.1242/dev.129.17.4159
75. Attalla S, Taifour T, Bui T, Muller W. Insights from transgenic mouse models of PyMT-induced breast cancer: recapitulating human breast cancer progression in vivo. Oncogene. 2021;40(3):475-491. Doi:10.1038/s41388-020-01560-0
76. Jiang Z, Deng T, Jones R, et al. Rb deletion in mouse mammary progenitors induces luminal-B or basal-like/EMT tumor subtypes depending on p53 status. Journal of Clinical Investigation. 2010;120(9):3296-3309. Doi:10.1172/JCI41490
77. Green JE, Shibata MA, Yoshidome K, et al. The C3(1)/SV40 T-antigen transgenic mouse model of mammary cancer: ductal epithelial cell targeting with multistage progression to carcinoma. Oncogene. 2000;19(8):1020-1027. Doi:10.1038/sj.onc.1203280
78. Serra R, Crowley MR. Mouse models of transforming growth factor β impact in breast development and cancer. Endocr Relat Cancer. 2005;12(4):749-760. Doi:10.1677/erc.1.00936
79. Pfefferle AD, Darr DB, Calhoun BC, Mott KR, Rosen JM, Perou CM. The MMTV-Wnt1 murine model produces two phenotypically distinct subtypes of mammary tumors with unique therapeutic responses to an EGFR inhibitor. Dis Model Mech. Published online January 1, 2019. Doi:10.1242/dmm.037192
80. Tilli MT, Frech MS, Steed ME, et al. Introduction of Estrogen Receptor-α into the tTA/TAg Conditional Mouse Model Precipitates the Development of Estrogen-Responsive Mammary Adenocarcinoma. Am J Pathol. 2003;163(5):1713-1719. Doi:10.1016/S0002-9440(10)63529-8
81. Hollern DP, Contreras CM, Dance-Barnes S, et al. A mouse model featuring tissue-specific deletion of p53 and Brca1 gives rise to mammary tumors with genomic and transcriptomic similarities to human basal-like breast cancer. Breast Cancer Res Treat. 2019;174(1):143-155. Doi:10.1007/s10549-018-5061-y
82. Doha ZO, Wang X, Calistri NL, et al. MYC Deregulation and PTEN Loss Model Tumor and Stromal Heterogeneity of Aggressive Triple-Negative Breast Cancer. Nat Commun. 2023;14(1):5665. Doi:10.1038/s41467-023-40841-6
83. Jones LM, Broz ML, Ranger JJ, et al. STAT3 Establishes an Immunosuppressive Microenvironment during the Early Stages of Breast Carcinogenesis to Promote Tumor Growth and Metastasis. Cancer Res. 2016;76(6):1416-1428. Doi:10.1158/0008-5472.CAN-15-2770
84. Hollern DP, Xu N, Thennavan A, et al. B Cells and T Follicular Helper Cells Mediate Response to Checkpoint Inhibitors in High Mutation Burden Mouse Models of Breast Cancer. Cell. 2019;179(5):1191-1206.e21. Doi:10.1016/j.cell.2019.10.028
85. Dobrolecki LE, Airhart SD, Alferez DG, et al. Patient-derived xenograft (PDX) models in basic and translational breast cancer research. Cancer and Metastasis Reviews. 2016;35(4):547-573. Doi:10.1007/s10555-016-9653-x
86. Lefley D, Howard F, Arshad F, et al. Development of clinically relevant in vivo metastasis models using human bone discs and breast cancer patient-derived xenografts. Breast Cancer Res. 2019;21(1):130. Doi:10.1186/s13058-019-1220-2
87. Pettersen S, Øy GF, Egeland EV, et al. Breast cancer patient-derived explant cultures recapitulate in vivo drug responses. Front Oncol. 2023;13. Doi:10.3389/fonc.2023.1040665
88. Choi Y, Lee S, Kim K, Kim SH, Chung YJ, Lee C. Studying cancer immunotherapy using patient-derived xenografts (PDXs) in humanized mice. Exp Mol Med. 2018;50(8):1-9. Doi:10.1038/s12276-018-0115-0
89. Masemann D, Ludwig S, Boergeling Y. Advances in Transgenic Mouse Models to Study Infections by Human Pathogenic Viruses. Int J Mol Sci. 2020;21(23):9289. Doi:10.3390/ijms21239289
90. Morton JJ, Bird G, Keysar SB, et al. XactMice: humanizing mouse bone marrow enables microenvironment reconstitution in a patient-derived xenograft model of head and neck cancer. Oncogene. 2016;35(3):290-300. Doi:10.1038/onc.2015.94
91. Wang M, Yao L, Cheng M, et al. Humanized mice in studying efficacy and mechanisms of PD‐1‐targeted cancer immunotherapy. The FASEB Journal. 2018;32(3):1537-1549. Doi:10.1096/fj.201700740R
92. Zhao Y, Shuen TWH, Toh TB, et al. Development of a new patient-derived xenograft humanised mouse model to study human-specific tumour microenvironment and immunotherapy. Gut. 2018;67(10):1845-1854. Doi:10.1136/gutjnl-2017-315201
93. Morton JJ, Alzofon N, Keysar SB, et al. Studying Immunotherapy Resistance in a Melanoma Autologous Humanized Mouse Xenograft. Molecular Cancer Research. 2021;19(2):346-357. Doi:10.1158/1541-7786.MCR-20-0686
94. Marín-Jiménez JA, Capasso A, Lewis MS, et al. Testing Cancer Immunotherapy in a Human Immune System Mouse Model: Correlating Treatment Responses to Human Chimerism, Therapeutic Variables and Immune Cell Phenotypes. Front Immunol. 2021;12. Doi:10.3389/fimmu.2021.607282
95. Pyo KH, Kim JH, Lee JM, et al. Promising preclinical platform for evaluation of immuno-oncology drugs using Hu-PBL-NSG lung cancer models. Lung Cancer. 2019;127:112-121. Doi:10.1016/j.lungcan.2018.11.035
96. Meraz IM, Majidi M, Meng F, et al. An Improved Patient-Derived Xenograft Humanized Mouse Model for Evaluation of Lung Cancer Immune Responses. Cancer Immunol Res. 2019;7(8):1267-1279. Doi:10.1158/2326-6066.CIR-18-0874
97. Kang Y, Armstrong AJ, Hsu DS. An autologous humanized patient-derived xenograft (PDX) model for evaluation of nivolumab immunotherapy in renal cell cancer: a case report. Stem Cell Investig. 2022;9:8-8. Doi:10.21037/sci-2022-029
98. Rosato RR, Dávila-González D, Choi DS, et al. Evaluation of anti-PD-1-based therapy against triple-negative breast cancer patient-derived xenograft tumors engrafted in humanized mouse models. Breast Cancer Research. 2018;20(1):108. Doi:10.1186/s13058-018-1037-4
99. Liu WN, Fong SY, Tan WWS, et al. Establishment and Characterization of Humanized Mouse NPC-PDX Model for Testing Immunotherapy. Cancers (Basel). 2020;12(4):1025. Doi:10.3390/cancers12041025
100. Rosato RR, Dávila-González D, Choi DS, et al. Evaluation of anti-PD-1-based therapy against triple-negative breast cancer patient-derived xenograft tumors engrafted in humanized mouse models. Breast Cancer Research. 2018;20(1):108. Doi:10.1186/s13058-018-1037-4
101. Loibl S, Poortmans P, Morrow M, Denkert C, Curigliano G. Breast cancer. The Lancet. 2021;397(10286):1750-1769. Doi:10.1016/S0140-6736(20)32381-3
102. Bruss C, Kellner K, Albert V, et al. Immune Checkpoint Profiling in Humanized Breast Cancer Mice Revealed Cell-Specific LAG-3/PD-1/TIM-3 Co-Expression and Elevated PD-1/TIM-3 Secretion. Cancers (Basel). 2023;15(9):2615. Doi:10.3390/cancers15092615
103. Scherer SD, Riggio AI, Haroun F, et al. An immune-humanized patient-derived xenograft model of estrogen-independent, hormone receptor positive metastatic breast cancer. Breast Cancer Research. 2021;23(1):100. Doi:10.1186/s13058-021-01476-x
104. Yu J, Qin B, Moyer AM, et al. Establishing and characterizing patient-derived xenografts using pre-chemotherapy percutaneous biopsy and post-chemotherapy surgical samples from a prospective neoadjuvant breast cancer study. Breast Cancer Research. 2017;19(1):130. Doi:10.1186/s13058-017-0920-8
105. Guillen KP, Fujita M, Butterfield AJ, et al. A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology. Nat Cancer. 2022;3(2):232-250. Doi:10.1038/s43018-022-00337-6
106. Liu Y, Wu W, Cai C, Zhang H, Shen H, Han Y. Patient-derived xenograft models in cancer therapy: technologies and applications. Signal Transduct Target Ther. 2023;8(1):160. Doi:10.1038/s41392-023-01419-2
107. Muraro MG, Muenst S, Mele V, et al. Ex-vivo assessment of drug response on breast cancer primary tissue with preserved microenvironments. Oncoimmunology. Published online May 30, 2017:e1331798. Doi:10.1080/2162402X.2017.1331798
108. Urbaniak A, Piña-Oviedo S, Yuan Y, Huczyński A, Chambers TC. Limitations of an ex vivo breast cancer model for studying the mechanism of action of the anticancer drug paclitaxel. Eur J Pharmacol. 2021;891:173780. Doi:10.1016/j.ejphar.2020.173780
109. Karekla E, Liao WJ, Sharp B, et al. Ex Vivo Explant Cultures of Non–Small Cell Lung Carcinoma Enable Evaluation of Primary Tumor Responses to Anticancer Therapy. Cancer Res. 2017;77(8):2029-2039. Doi:10.1158/0008-5472.CAN-16-1121
110. Yang R, Yu Y. Patient-derived organoids in translational oncology and drug screening. Cancer Lett. 2023;562:216180. Doi:10.1016/j.canlet.2023.216180
111. Sachs N, de Ligt J, Kopper O, et al. A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity. Cell. 2018;172(1-2):373-386.e10. Doi:10.1016/j.cell.2017.11.010
112. Peng D, Gleyzer R, Tai WH, et al. Evaluating the transcriptional fidelity of cancer models. Genome Med. 2021;13(1):73. Doi:10.1186/s13073-021-00888-w
113. Chakrabarti J, Koh V, So JBY, Yong WP, Zavros Y. A Preclinical Human-Derived Autologous Gastric Cancer Organoid/Immune Cell Co-Culture Model to Predict the Efficacy of Targeted Therapies. Journal of Visualized Experiments. 2021;(173). Doi:10.3791/61443
114. Tsai S, McOlash L, Palen K, et al. Development of primary human pancreatic cancer organoids, matched stromal and immune cells and 3D tumor microenvironment models. BMC Cancer. 2018;18(1):335. Doi:10.1186/s12885-018-4238-4
115. Michie J, Beavis PA, Freeman AJ, et al. Antagonism of IAPs Enhances CAR T-cell Efficacy. Cancer Immunol Res. 2019;7(2):183-192. Doi:10.1158/2326-6066.CIR-18-0428
116. Jenkins RW, Aref AR, Lizotte PH, et al. Ex Vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids. Cancer Discov. 2018;8(2):196-215. Doi:10.1158/2159-8290.CD-17-0833
117. Snijder B, Vladimer GI, Krall N, et al. Image-based ex-vivo drug screening for patients with aggressive haematological malignancies: interim results from a single-arm, open-label, pilot study. Lancet Haematol. 2017;4(12):e595-e606. Doi:10.1016/S2352-3026(17)30208-9
118. Williams ST, Wells G, Conroy S, et al. Precision oncology using ex vivo technology: a step towards individualised cancer care? Expert Rev Mol Med. 2022;24:e39. Doi:10.1017/erm.2022.32
119. Ladan MM, Meijer TG, Verkaik NS, et al. Functional Ex Vivo Tissue-Based Chemotherapy Sensitivity Testing for Breast Cancer. Cancers (Basel). 2022;14(5):1252. Doi:10.3390/cancers14051252
120. Ladan MM, Meijer TG, Verkaik NS, et al. Proof-of-concept study linking ex vivo sensitivity testing to neoadjuvant anthracycline-based chemotherapy response in breast cancer patients. NPJ Breast Cancer. 2023;9(1):80. Doi:10.1038/s41523-023-00583-6
121. Jordan VC. 50th anniversary of the first clinical trial with ICI 46,474 (tamoxifen): then what happened? Endocr Relat Cancer. 2021;28(1):R11-R30. Doi:10.1530/ERC-20-0335
122. David Shaywitz. The Startling History Behind Merck’s New Cancer Blockbuster. Forbes Magazine