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Anti-Cancer Drug Validation: the Contribution of Tissue Engineered Models

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Abstract

Drug toxicity frequently goes concealed until clinical trials stage, which is the most challenging, dangerous and expensive stage of drug development. Both the cultures of cancer cells in traditional 2D assays and animal studies have limitations that cannot ever be unraveled by improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. Considering the NCI60, a panel of 60 cancer cell lines representative of 9 different cancer types: leukemia, lung, colorectal, central nervous system (CNS), melanoma, ovarian, renal, prostate and breast, we propose to review current “state of art” on the 9 cancer types specifically addressing the 3D tissue models that have been developed and used in drug discovery processes as an alternative to complement their study.

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References

  1. Calvert, H. (2014). Cancer Drug Design and Discovery. In S. Neidle (Ed.), Cancer Drug Design and Discovery (Second ed., pp. xi–xiii). San Diego: Academic Press.

    Chapter  Google Scholar 

  2. Alemany-Ribes, M., & Semino, C. E. (2014). Bioengineering 3D environments for cancer models. Advanced Drug Delivery Reviews, 79-80, 40–49.

    Article  CAS  PubMed  Google Scholar 

  3. WHO. Essential drugs for cancer chemotherapy. (1994). WHO consultation. Bulletin of the World Health Organization, 72, 693–698.

    Google Scholar 

  4. Burger, A., & Fiebig, H.-H. (2004). Preclinical screening for new anticancer agents. In H. McLeod (Ed.), Figg W (pp. 29–44). Handbook of Anticancer Pharmacokinetics and Pharmacodynamics: Humana Press.

    Google Scholar 

  5. Burger, A. M., & Fiebig, H.-H. (2014). Preclinical screening for new anticancer agents. Handbook of Anticancer Pharmacokinetics and Pharmacodynamics: Springer, 23–38.

  6. Nietzer, S., Dandekar, G., Walles, H., Wasik, M. (2012). Three dimensional tissue models for research in oncology: INTECH open access Publisher.

  7. Hutchinson, L., & Kirk, R. (2011). High drug attrition rates--where are we going wrong? Nature Reviews. Clinical Oncology, 8, 189–190.

    Article  PubMed  Google Scholar 

  8. Blatt, N. L., Mingaleeva, R. N., Solovieva, V. V., Khaiboullina, S. F., Lombardi, V. C., & Rizvanov, A. A. (2013). Application of cell and tissue culture systems for anticancer drug screening. World Applied Sciences Journal, 23, 315–325.

    Google Scholar 

  9. Shoemaker, R. H. (2006). The NCI60 human tumour cell line anticancer drug screen. Nature Reviews Cancer, 6, 813–823.

    Article  CAS  PubMed  Google Scholar 

  10. Ross, D. T., Scherf, U., Eisen, M. B., et al. (2000). Systematic variation in gene expression patterns in human cancer cell lines. Nature Genetics, 24, 227–235.

    Article  CAS  PubMed  Google Scholar 

  11. Van Staveren W, Solís DW, Hebrant A, Detours V, Dumont JE, Maenhaut C. (2009). Human cancer cell lines: Experimental models for cancer cells in situ? For cancer stem cells? Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1795, 92–103.

  12. Ridky, T. W., Chow, J. M., Wong, D. J., & Khavari, P. A. (2010). Invasive three-dimensional organotypic neoplasia from multiple normal human epithelia. Nature Medicine, 16, 1450–1455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Feder-Mengus, C., Ghosh, S., Reschner, A., Martin, I., & Spagnoli, G. C. (2008). New dimensions in tumor immunology: what does 3D culture reveal? Trends in Molecular Medicine, 14, 333–340.

    Article  CAS  PubMed  Google Scholar 

  14. Gurski, L. A., Jha, A. K., Zhang, C., Jia, X., & Farach-Carson, M. C. (2009). Hyaluronic acid-based hydrogels as 3D matrices for in vitro evaluation of chemotherapeutic drugs using poorly adherent prostate cancer cells. Biomaterials, 30, 6076–6085.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gorlach, A., Herter, P., Hentschel, H., Frosch, P. J., & Acker, H. (1994). Effects of nIFN beta and rIFN gamma on growth and morphology of two human melanoma cell lines: comparison between two- and three-dimensional culture. International Journal of Cancer:Journal International du Cancer, 56, 249–254.

    Article  CAS  PubMed  Google Scholar 

  16. Chignola, R., Schenetti, A., Andrighetto, G., et al. (2000). Forecasting the growth of multicell tumour spheroids: implications for the dynamic growth of solid tumours. Cell Proliferation, 33, 219–229.

    Article  CAS  PubMed  Google Scholar 

  17. Wozniak, M. A., Modzelewska, K., Kwong, L., & Keely, P. J. (2004). Focal adhesion regulation of cell behavior. Biochimica et Biophysica Acta, 1692, 103–119.

    Article  CAS  PubMed  Google Scholar 

  18. Cheema, U., Brown, R. A., Alp, B., & MacRobert, A. J. (2008). Spatially defined oxygen gradients and vascular endothelial growth factor expression in an engineered 3D cell model. Cellular and Molecular Life Sciences: CMLS, 65, 177–186.

    Article  CAS  PubMed  Google Scholar 

  19. Yamazaki, D., Kurisu, S., & Takenawa, T. (2009). Involvement of Rac and rho signaling in cancer cell motility in 3D substrates. Oncogene, 28, 1570–1583.

    Article  CAS  PubMed  Google Scholar 

  20. David, L., Dulong, V., Le Cerf, D., Cazin, L., Lamacz, M., & Vannier, J. P. (2008). Hyaluronan hydrogel: an appropriate three-dimensional model for evaluation of anticancer drug sensitivity. Acta Biomaterialia, 4, 256–263.

    Article  CAS  PubMed  Google Scholar 

  21. Horning, J. L., Sahoo, S. K., Vijayaraghavalu, S., et al. (2008). 3-D tumor model for in vitro evaluation of anticancer drugs. Molecular Pharmaceutics, 5, 849–862.

    Article  CAS  PubMed  Google Scholar 

  22. Serebriiskii, I., Castello-Cros, R., Lamb, A., Golemis, E. A., & Cukierman, E. (2008). Fibroblast-derived 3D matrix differentially regulates the growth and drug-responsiveness of human cancer cells. Matrix biology : journal of the International Society for Matrix Biology, 27, 573–585.

    Article  CAS  Google Scholar 

  23. Wenzel, C., Riefke, B., Grundemann, S., et al. (2014). 3D high-content screening for the identification of compounds that target cells in dormant tumor spheroid regions. Experimental Cell Research, 323, 131–143.

    Article  CAS  PubMed  Google Scholar 

  24. Ratner B HA, Schoen F, Lemons J. (2004). Biomaterials science in: Elsevier Academic Press, ed. 3rd edition ed. San Diego.

  25. Rimann, M., & Graf-Hausner, U. (2012). Synthetic 3D multicellular systems for drug development. Current Opinion in Biotechnology, 23, 803–809.

    Article  CAS  PubMed  Google Scholar 

  26. Carvalho, M. R., Lima, D., Reis, R. L., Correlo, V. M., & Oliveira, J. M. (2015). Evaluating biomaterial- and microfluidic-based 3D tumor models. Trends in Biotechnology, 33, 667–678.

    Article  CAS  PubMed  Google Scholar 

  27. Elliott, N. T., & Yuan, F. (2011). A review of three-dimensional in vitro tissue models for drug discovery and transport studies. Journal of Pharmaceutical Sciences, 100, 59–74.

    Article  CAS  PubMed  Google Scholar 

  28. Peck, Y., & Wang, D. A. (2013). Three-dimensionally engineered biomimetic tissue models for in vitro drug evaluation: delivery, efficacy and toxicity. Expert Opinion on Drug Delivery, 10, 369–383.

    Article  CAS  PubMed  Google Scholar 

  29. Tredan, O., Galmarini, C. M., Patel, K., & Tannock, I. F. (2007). Drug resistance and the solid tumor microenvironment. Journal of the National Cancer Institute, 99, 1441–1454.

    Article  CAS  PubMed  Google Scholar 

  30. Nyga, A., Cheema, U., & Loizidou, M. (2011). 3D tumour models: novel in vitro approaches to cancer studies. Journal of cell communication and signaling, 5, 239–248.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Fennema, E., Rivron, N., Rouwkema, J., van Blitterswijk, C., & de Boer, J. (2013). Spheroid culture as a tool for creating 3D complex tissues. Trends in Biotechnology, 31, 108–115.

    Article  CAS  PubMed  Google Scholar 

  32. Chen, Y. A., King, A. D., Shih, H. C., et al. (2011). Generation of oxygen gradients in microfluidic devices for cell culture using spatially confined chemical reactions. Lab on a Chip, 11, 3626–3633.

    Article  CAS  PubMed  Google Scholar 

  33. Tung, Y. C., Hsiao, A. Y., Allen, S. G., Torisawa, Y. S., Ho, M., & Takayama, S. (2011). High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array. The Analyst, 136, 473–478.

    Article  CAS  PubMed  Google Scholar 

  34. Blehm, B. H., Jiang, N., Kotobuki, Y., & Tanner, K. (2015). Deconstructing the role of the ECM microenvironment on drug efficacy targeting MAPK signaling in a pre-clinical platform for cutaneous melanoma. Biomaterials, 56, 129–139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Vorsmann, H., Groeber, F., Walles, H., et al. (2013). Development of a human three-dimensional organotypic skin-melanoma spheroid model for in vitro drug testing. Cell Death & Disease, 4, e719.

    Article  CAS  Google Scholar 

  36. Loessner, D., Stok, K. S., Lutolf, M. P., Hutmacher, D. W., Clements, J. A., & Rizzi, S. C. (2010). Bioengineered 3D platform to explore cell-ECM interactions and drug resistance of epithelial ovarian cancer cells. Biomaterials, 31, 8494–8506.

    Article  CAS  PubMed  Google Scholar 

  37. Loessner, D., Rizzi, S. C., Stok, K. S., et al. (2013). A bioengineered 3D ovarian cancer model for the assessment of peptidase-mediated enhancement of spheroid growth and intraperitoneal spread. Biomaterials, 34, 7389–7400.

    Article  CAS  PubMed  Google Scholar 

  38. Raghavan, S., Ward, M. R., Rowley, K. R., et al. (2015). Formation of stable small cell number three-dimensional ovarian cancer spheroids using hanging drop arrays for preclinical drug sensitivity assays. Gynecologic Oncology, 138, 181–189.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. DesRochers, T. M., Suter, L., Roth, A., & Kaplan, D. L. (2013). Bioengineered 3D human kidney tissue, a platform for the determination of nephrotoxicity. PloS One, 8, e59219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Leeper, A. D., Farrell, J., Williams, L. J., et al. (2012). Determining tamoxifen sensitivity using primary breast cancer tissue in collagen-based three-dimensional culture. Biomaterials, 33, 907–915.

    Article  CAS  PubMed  Google Scholar 

  41. Dhiman, H. K., Ray, A. R., & Panda, A. K. (2005). Three-dimensional chitosan scaffold-based MCF-7 cell culture for the determination of the cytotoxicity of tamoxifen. Biomaterials, 26, 979–986.

    Article  CAS  PubMed  Google Scholar 

  42. Li, Q., Chen, C., Kapadia, A., et al. (2011). 3D models of epithelial-mesenchymal transition in breast cancer metastasis: high-throughput screening assay development, validation, and pilot screen. Journal of Biomolecular Screening, 16, 141–154.

    Article  CAS  PubMed  Google Scholar 

  43. Wang, Y. C., Chao, T. K., Chang, C. C., Yo, Y. T., Yu, M. H., & Lai, H. C. (2013). Drug screening identifies niclosamide as an inhibitor of breast cancer stem-like cells. PloS One, 8, e74538.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Li, Q., Chow, A. B., & Mattingly, R. R. (2010). Three-dimensional overlay culture models of human breast cancer reveal a critical sensitivity to mitogen-activated protein kinase kinase inhibitors. The Journal of Pharmacology and Experimental Therapeutics, 332, 821–828.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Lan, S. F., & Starly, B. (2011). Alginate based 3D hydrogels as an in vitro co-culture model platform for the toxicity screening of new chemical entities. Toxicology and Applied Pharmacology, 256, 62–72.

    Article  CAS  PubMed  Google Scholar 

  46. de la Puente, P., Muz, B., Gilson, R. C., et al. (2015). 3D tissue-engineered bone marrow as a novel model to study pathophysiology and drug resistance in multiple myeloma. Biomaterials, 73, 70–84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Luca, A. C., Mersch, S., Deenen, R., et al. (2013). Impact of the 3D microenvironment on phenotype, gene expression, and EGFR inhibition of colorectal cancer cell lines. PloS One, 8, e59689.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Mohanty, C., Fayad, W., Olofsson, M. H., et al. (2013). Massive induction of apoptosis of multicellular tumor spheroids by a novel compound with a calmodulin inhibitor-like mechanism. Journal of Cancer Therapeutics and Research, 2.

  49. Hirt, C., Papadimitropoulos, A., Muraro, M. G., et al. (2015). Bioreactor-engineered cancer tissue-like structures mimic phenotypes, gene expression profiles and drug resistance patterns observed "in vivo". Biomaterials, 62, 138–146.

    Article  CAS  PubMed  Google Scholar 

  50. Weiswald, L. B., Richon, S., Massonnet, G., et al. (2013). A short-term colorectal cancer sphere culture as a relevant tool for human cancer biology investigation. British Journal of Cancer, 108, 1720–1731.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Chen, Y., Gao, D., Liu, H., Lin, S., & Jiang, Y. (2015). Drug cytotoxicity and signaling pathway analysis with three-dimensional tumor spheroids in a microwell-based microfluidic chip for drug screening. Analytica Chimica Acta, 898, 85–92.

    Article  CAS  PubMed  Google Scholar 

  52. Dolznig, H., Rupp, C., Puri, C., et al. (2011). Modeling colon adenocarcinomas in vitro a 3D co-culture system induces cancer-relevant pathways upon tumor cell and stromal fibroblast interaction. The American Journal of Pathology, 179, 487–501.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Kim, T. E., Kim, C. G., Kim, J. S., et al. (2016). Three-dimensional culture and interaction of cancer cells and dendritic cells in an electrospun nano-submicron hybrid fibrous scaffold. International Journal of Nanomedicine, 11, 823–835.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Erguven, M., Yazihan, N., Aktas, E., et al. (2010). Carvedilol in glioma treatment alone and with imatinib in vitro. International Journal of Oncology, 36, 857–866.

    Article  CAS  PubMed  Google Scholar 

  55. Qin, L., Wang, C. Z., Fan, H. J., et al. (2014). A dual-targeting liposome conjugated with transferrin and arginine-glycine-aspartic acid peptide for glioma-targeting therapy. Oncology Letters, 8, 2000–2006.

    PubMed  PubMed Central  Google Scholar 

  56. Xu, Z., Gao, Y., Hao, Y., et al. (2013). Application of a microfluidic chip-based 3D co-culture to test drug sensitivity for individualized treatment of lung cancer. Biomaterials, 34, 4109–4117.

    Article  CAS  PubMed  Google Scholar 

  57. Stratmann, A. T., Fecher, D., Wangorsch, G., et al. (2014). Establishment of a human 3D lung cancer model based on a biological tissue matrix combined with a Boolean in silico model. Molecular Oncology, 8, 351–365.

    Article  CAS  PubMed  Google Scholar 

  58. Chambers, K. F., Mosaad, E. M., Russell, P. J., Clements, J. A., & Doran, M. R. (2015). Correction: 3D cultures of prostate cancer cells cultured in a novel high-throughput culture platform are more resistant to chemotherapeutics compared to cells cultured in monolayer. PloS One, 10, e0125641.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Evensen, N. A., Li, J., Yang, J., et al. (2013). Development of a high-throughput three-dimensional invasion assay for anti-cancer drug discovery. PloS One, 8, e82811.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Lui, P., Cashin, R., Machado, M., Hemels, M., Corey-Lisle, P. K., & Einarson, T. R. (2007). Treatments for metastatic melanoma: synthesis of evidence from randomized trials. Cancer Treatment Reviews, 33, 665–680.

    Article  PubMed  Google Scholar 

  61. Kyrgidis, A., Valasidis, A., Bourlidou, E., & Andreadis, C. (2011). Better targeting melanoma: options beyond surgery and conventional chemotherapy. Recent Patents on Endocrine, Metabolic & Immune Drug Discovery, 5, 147–159.

    Article  CAS  Google Scholar 

  62. Spagnolo, F., & Queirolo, P. (2012). Upcoming strategies for the treatment of metastatic melanoma. Archives of Dermatological Research, 304, 177–184.

    Article  CAS  PubMed  Google Scholar 

  63. Folkman, J. (1990). What is the evidence that tumors are angiogenesis dependent? Journal of the National Cancer Institute, 82, 4–6.

    Article  CAS  PubMed  Google Scholar 

  64. Liotta, L. A., Kleinerman, J., & Saidel, G. M. (1974). Quantitative relationships of intravascular tumor cells, tumor vessels, and pulmonary metastases following tumor implantation. Cancer Research, 34, 997–1004.

    CAS  PubMed  Google Scholar 

  65. Groeber, F., Holeiter, M., Hampel, M., Hinderer, S., & Schenke-Layland, K. (2011). Skin tissue engineering--in vivo and in vitro applications. Advanced Drug Delivery Reviews, 63, 352–366.

    Article  CAS  PubMed  Google Scholar 

  66. Mehta, G., Hsiao, A. Y., Ingram, M., Luker, G. D., & Takayama, S. (2012). Opportunities and challenges for use of tumor spheroids as models to test drug delivery and efficacy. Journal of Controlled Release: Official Journal of the Controlled Release Society, 164, 192–204.

    Article  CAS  Google Scholar 

  67. Ramgolam, K., Lauriol, J., Lalou, C., et al. (2011). Melanoma spheroids grown under neural crest cell conditions are highly plastic migratory/invasive tumor cells endowed with immunomodulator function. PloS One, 6, e18784.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Jemal, A., Bray, F., Center, M. M., Ferlay, J., Ward, E., & Forman, D. (2011). Global cancer statistics. CA: A Cancer Journal for Clinicians, 61, 69–90.

    Google Scholar 

  69. Piccart, M., Lamb, H., & Vermorken, J. B. (2001). Current and future potential roles of the platinum drugs in the treatment of ovarian cancer. Annals of Oncology, 12, 1195–1203.

    Article  CAS  PubMed  Google Scholar 

  70. Guppy, A. E., Nathan, P. D., & Rustin, G. J. (2005). Epithelial ovarian cancer: a review of current management. Clinical Oncology, 17, 399–411.

    Article  CAS  PubMed  Google Scholar 

  71. Kenny, H. A., Dogan, S., Zillhardt, M., et al. (2009). Organotypic models of metastasis: a three-dimensional culture mimicking the human peritoneum and omentum for the study of the early steps of ovarian cancer metastasis. Cancer Treatment and Research, 149, 335–351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Grun, B., Benjamin, E., Sinclair, J., et al. (2009). Three-dimensional in vitro cell biology models of ovarian and endometrial cancer. Cell Proliferation, 42, 219–228.

    Article  CAS  PubMed  Google Scholar 

  73. Shield, K., Ackland, M. L., Ahmed, N., & Rice, G. E. (2009). Multicellular spheroids in ovarian cancer metastases: biology and pathology. Gynecologic Oncology, 113, 143–148.

    Article  PubMed  Google Scholar 

  74. Cohen, H. T., & McGovern, F. J. (2005). Renal-cell carcinoma. New England Journal of Medicine, 353, 2477–2490.

    Article  CAS  PubMed  Google Scholar 

  75. McLaughlin, J. K., Lipworth, L., Tarone, R. E. (2006). Epidemiologic aspects of renal cell carcinoma. Seminars in oncology; Elsevier. p. 527–33.

  76. Harris, D. T. (1983). Hormonal therapy and chemotherapy of renal-cell carcinoma. Seminars in Oncology, 10, 422–430.

    CAS  PubMed  Google Scholar 

  77. Yagoda, A., & Bander, N. H. (1989). Failure of cytotoxic chemotherapy, 1983-1988, and the emerging role of monoclonal antibodies for renal cancer. Urologia Internationalis, 44, 338–345.

    Article  CAS  PubMed  Google Scholar 

  78. Yang, J. C., & Childs, R. (2006). Immunotherapy for renal cell cancer. Journal of Clinical Oncology, 24, 5576–5583.

    Article  CAS  PubMed  Google Scholar 

  79. Wang, P.-C., & Takezawa, T. (2005). Reconstruction of renal glomerular tissue using collagen vitrigel scaffold. Journal of Bioscience and Bioengineering, 99, 529–540.

    Article  CAS  PubMed  Google Scholar 

  80. Perin, L., Da Sacco, S., & De Filippo, R. E. (2011). Regenerative medicine of the kidney. Advanced Drug Delivery Reviews, 63, 379–387.

    Article  CAS  PubMed  Google Scholar 

  81. Peloso, A., Katari, R., Patel, T., et al. (2013). Considerations on the development of a model of kidney bioengineering and regeneration in rats. Expert Review of Medical Devices, 10, 597–601.

    Article  CAS  PubMed  Google Scholar 

  82. Yao, X., Panichpisal, K., Kurtzman, N., & Nugent, K. (2007). Cisplatin nephrotoxicity: a review. The American Journal of the Medical Sciences, 334, 115–124.

    Article  PubMed  Google Scholar 

  83. Astashkina, A. I., Mann, B. K., Prestwich, G. D., & Grainger, D. W. (2012). A 3-D organoid kidney culture model engineered for high-throughput nephrotoxicity assays. Biomaterials, 33, 4700–4711.

    Article  CAS  PubMed  Google Scholar 

  84. Song, J. J., Guyette, J. P., Gilpin, S. E., Gonzalez, G., Vacanti, J. P., & Ott, H. C. (2013). Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nature Medicine, 19, 646–651.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Bissell, M. J. (2007). Modelling molecular mechanisms of breast cancer and invasion: lessons from the normal gland. Biochemical Society Transactions, 35, 18–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Lee, E., Parry, G., & Bissell, M. J. (1984). Modulation of secreted proteins of mouse mammary epithelial cells by the collagenous substrata. The Journal of Cell Biology, 98, 146–155.

    Article  CAS  PubMed  Google Scholar 

  87. Streuli, C. H., & Bissell, M. J. (1990). Expression of extracellular matrix components is regulated by substratum. The Journal of Cell Biology, 110, 1405–1415.

    Article  CAS  PubMed  Google Scholar 

  88. Schmeichel, K. L., & Bissell, M. J. (2003). Modeling tissue-specific signaling and organ function in three dimensions. Journal of Cell Science, 116, 2377–2388.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Petersen, O. W., Ronnov-Jessen, L., Howlett, A. R., & Bissell, M. J. (1992). Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells. Proceedings of the National Academy of Sciences of the United States of America, 89, 9064–9068.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Szot, C. S., Buchanan, C. F., Freeman, J. W., & Rylander, M. N. (2011). 3D in vitro bioengineered tumors based on collagen I hydrogels. Biomaterials, 32, 7905–7912.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Li, Q., Mullins, S. R., Sloane, B. F., & Mattingly, R. R. (2008). p21-activated kinase 1 coordinates aberrant cell survival and pericellular proteolysis in a three-dimensional culture model for premalignant progression of human breast cancer. Neoplasia, 10, 314–329.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Bonnet, D., & Dick, J. E. (1997). Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature Medicine, 3, 730–737.

    Article  CAS  PubMed  Google Scholar 

  93. Reya, T., Morrison, S. J., Clarke, M. F., & Weissman, I. L. (2001). Stem cells, cancer, and cancer stem cells. Nature, 414, 105–111.

    Article  CAS  PubMed  Google Scholar 

  94. Clarke, M. F., & Fuller, M. (2006). Stem cells and cancer: two faces of eve. Cell, 124, 1111–1115.

    Article  CAS  PubMed  Google Scholar 

  95. van Vliet, E. (2011). Current standing and future prospects for the technologies proposed to transform toxicity testing in the twenty-first century. ALTEX, 28, 17–44.

    Article  PubMed  Google Scholar 

  96. Hodge, A. C., Fenster, A., Downey, D. B., & Ladak, H. M. (2006). Prostate boundary segmentation from ultrasound images using 2D active shape models: optimisation and extension to 3D. Computer Methods and Programs in Biomedicine, 84, 99–113.

    Article  PubMed  Google Scholar 

  97. Curtin, P., Youm, H., & Salih, E. (2012). Three-dimensional cancer-bone metastasis model using ex-vivo co-cultures of live calvarial bones and cancer cells. Biomaterials, 33, 1065–1078.

    Article  CAS  PubMed  Google Scholar 

  98. Florczyk, S. J., Liu, G., Kievit, F. M., Lewis, A. M., Wu, J. D., & Zhang, M. (2012). 3D porous chitosan-alginate scaffolds: a new matrix for studying prostate cancer cell-lymphocyte interactions in vitro. Advanced Healthcare Materials, 1, 590–599.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Bakker, E., Qattan, M., Mutti, L., Demonacos, C., Krstic-Demonacos, M. (2015). The role of microenvironment and immunity in drug response in leukemia. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research.

  100. Moses, B.S., Slone, W.L., Thomas, P., et al. (2015). Bone marrow microenvironment modulation of acute lymphoblastic leukemia phenotype. Experimental hematology.

  101. Qureshi, A. K., & Hall, G. W. (2013). Leukaemias: a review. Paediatrics & Child Health, 23, 461–466.

    Article  Google Scholar 

  102. Bakker, E., Qattan, M., Mutti, L., Demonacos, C., Krstic-Demonacos, M. (2016). The role of microenvironment and immunity in drug response in leukemia. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1863, 414–426.

  103. Sison, E.A.R., & Brown, P. (2011). The bone marrow microenvironment and leukemia: Biology and therapeutic targeting. Expert review of hematology, 4, 271–283

  104. Iwamoto, S., Mihara, K., Downing, J. R., Pui, C.-H., & Campana, D. (2007). Mesenchymal cells regulate the response of acute lymphoblastic leukemia cells to asparaginase. Journal of Clinical Investigation, 117, 1049.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Usuludin, S. B., Cao, X., & Lim, M. (2012). Co-culture of stromal and erythroleukemia cells in a perfused hollow fiber bioreactor system as an in vitro bone marrow model for myeloid leukemia. Biotechnology and Bioengineering, 109, 1248–1258.

    Article  CAS  PubMed  Google Scholar 

  106. Vaiselbuh, S. R., Edelman, M., Lipton, J. M., & Liu, J. M. (2010). Ectopic human mesenchymal stem cell-coated scaffolds in NOD/SCID mice: an in vivo model of the leukemia niche. Tissue engineering Part C, Methods, 16, 1523–1531.

    Article  CAS  PubMed  Google Scholar 

  107. Blanco, T. M., Mantalaris, A., Bismarck, A., & Panoskaltsis, N. (2010). The development of a three-dimensional scaffold for ex vivo biomimicry of human acute myeloid leukaemia. Biomaterials, 31, 2243–2251.

    Article  CAS  PubMed  Google Scholar 

  108. Marko-Varga, G., Fehniger, T. E., Rezeli, M., Döme, B., Laurell, T., & Végvári, Á. (2011). Drug localization in different lung cancer phenotypes by MALDI mass spectrometry imaging. Journal of Proteomics, 74, 982–992.

    Article  CAS  PubMed  Google Scholar 

  109. Huh, D., Matthews, B. D., Mammoto, A., Montoya-Zavala, M., Hsin, H. Y., & Ingber, D. E. (2010). Reconstituting organ-level lung functions on a chip. Science, 328, 1662–1668.

    Article  CAS  PubMed  Google Scholar 

  110. Fleming, M., Ravula, S., Tatishchev, S. F., & Wang, H. L. (2012). Colorectal carcinoma: pathologic aspects. Journal of gastrointestinal oncology, 3, 153–173.

    PubMed  PubMed Central  Google Scholar 

  111. Weiswald, L. B., Richon, S., Validire, P., et al. (2009). Newly characterised ex vivo colospheres as a three-dimensional colon cancer cell model of tumour aggressiveness. British Journal of Cancer, 101, 473–482.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Hopkins, A. M., DeSimone, E., Chwalek, K., & Kaplan, D. L. (2015). 3D in vitro modeling of the central nervous system. Progress in Neurobiology, 125, 1–25.

    Article  PubMed  Google Scholar 

  113. Shoffstall, A. J., Taylor, D. M., & Lavik, E. B. (2012). Engineering therapies in the CNS: what works and what can be translated. Neuroscience Letters, 519, 147–154.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Gladson, C. L. (1999). The extracellular matrix of gliomas: modulation of cell function. Journal of Neuropathology and Experimental Neurology, 58, 1029–1040.

    Article  CAS  PubMed  Google Scholar 

  115. Ananthanarayanan, B., Kim, Y., & Kumar, S. (2011). Elucidating the mechanobiology of malignant brain tumors using a brain matrix-mimetic hyaluronic acid hydrogel platform. Biomaterials, 32, 7913–7923.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Fedrigo, C. A., Grivicich, I., Schunemann, D. P., et al. (2011). Radioresistance of human glioma spheroids and expression of HSP70, p53 and EGFr. Radiation Oncology, 6, 156.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Jin, S. G., Jeong, Y. I., Jung, S., Ryu, H. H., Jin, Y. H., & Kim, I. Y. (2009). The effect of hyaluronic acid on the invasiveness of malignant glioma cells : comparison of invasion potential at hyaluronic acid hydrogel and matrigel. Journal of Korean Neurosurgical Society, 46, 472–478.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Coquerel, B., Poyer, F., Torossian, F., et al. (2009). Elastin-derived peptides: matrikines critical for glioblastoma cell aggressiveness in a 3-D system. Glia, 57, 1716–1726.

    Article  PubMed  Google Scholar 

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Acknowledgements

This article is a result of the project FROnTHERA (NORTE-01-0145-FEDER-000023), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This articlewas also supported by the EU Framework Programme for Research and Innovation HORIZON 2020 (H2020) under grant agreement n° 668983 — FoReCaST. FCT distinction attributed to Joaquim M. Oliveira (IF/00423/2012) and Vitor M. Correlo (IF/01214/2014) under the Investigator FCT program is also greatly acknowledged.

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Authors and Affiliations

  1. 3B’s Research Group - Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, AvePark, 4806-909 Taipas, Guimarães, Portugal

    Mariana R. Carvalho, Daniela Lima, Rui L. Reis, Joaquim M. Oliveira & Vitor M. Correlo

  2. ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal

    Mariana R. Carvalho, Daniela Lima, Rui L. Reis, Joaquim M. Oliveira & Vitor M. Correlo

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  1. Mariana R. Carvalho
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  2. Daniela Lima
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  3. Rui L. Reis
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  4. Joaquim M. Oliveira
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  5. Vitor M. Correlo
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Correspondence to Rui L. Reis.

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Joaquim M. Oliveira and Vitor M. Correlo are Senior authors

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Carvalho, M.R., Lima, D., Reis, R.L. et al. Anti-Cancer Drug Validation: the Contribution of Tissue Engineered Models. Stem Cell Rev and Rep 13, 347–363 (2017). https://doi.org/10.1007/s12015-017-9720-x

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