Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Cancer-on-a-chip for Drug Screening

Author(s): I-Chi Lee*

Volume 24, Issue 45, 2018

Page: [5407 - 5418] Pages: 12

DOI: 10.2174/1381612825666190206235233

Price: $65

Abstract

The oncology pharmaceutical research spent a shocking amount of money on target validation and drug optimization in preclinical models because many oncology drugs fail during clinical trial phase III. One of the most important reasons for oncology drug failures in clinical trials may due to the poor predictive tool of existing preclinical models. Therefore, in cancer research and personalized medicine field, it is critical to improve the effectiveness of preclinical predictions of the drug response of patients to therapies and to reduce costly failures in clinical trials. Three dimensional (3D) tumor models combine micro-manufacturing technologies mimic critical physiologic parameters present in vivo, including complex multicellular architecture with multicellular arrangement and extracellular matrix deposition, packed 3D structures with cell–cell interactions, such as tight junctions, barriers to mass transport of drugs, nutrients and other factors, which are similar to in vivo tumor tissues. These systems provide a solution to mimic the physiological environment for improving predictive accuracy in oncology drug discovery.

This review gives an overview of the innovations, development and limitations of different types of tumor-like construction techniques such as self-assemble spheroid formation, spheroids formation by micro-manufacturing technologies, micro-dissected tumor tissues and tumor organoid. Combination of 3D tumor-like construction and microfluidic techniques to achieve tumor on a chip for in vitro tumor environment modeling and drug screening were all included. Eventually, developmental directions and technical challenges in the research field are also discussed. We believe tumor on chip models have provided better sufficient clinical predictive power and will bridge the gap between proof-of-concept studies and a wider implementation within the oncology drug development for pathophysiological applications.

Keywords: Three dimensional (3D) tumor model, sphere formation, micro-manufacturing technologies, microfluidic system, tumor organoids, on chip.

« Previous Next »
[1]
Scannell JW, Blanckley A, Boldon H, Warrington B. Diagnosing the decline in pharmaceutical R&D efficiency. Nat Rev Drug Discov 2012; 11(3): 191-200.
[2]
Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J. Clinical development success rates for investigational drugs. Nat Biotechnol 2014; 32(1): 40-51.
[3]
DiMasi JA, Grabowski HG. Economics of new oncology drug development. J Clin Oncol 2007; 25(2): 209-16.
[4]
Matsusaki M, Case CP, Akashi M. Three-dimensional cell culture technique and pathophysiology. Adv Drug Deliv Rev 2014; 74: 95-103.
[5]
Ugurel S, Schadendorf D, Pföhler C, et al. In vitro drug sensitivity predicts response and survival after individualized sensitivity-directed chemotherapy in metastatic melanoma: A multicenter phase II trial of the Dermatologic Cooperative Oncology Group. Clin Cancer Res 2006; 12(18): 5454-63.
[6]
Carstens MR, Fisher RC, Acharya AP, et al. Drug-eluting microarrays to identify effective chemotherapeutic combinations targeting patient-derived cancer stem cells. Proc Natl Acad Sci USA 2015; 112(28): 8732-7.
[7]
Mathews LA, Keller JM, Goodwin BL, et al. A 1536-well quantitative high-throughput screen to identify compounds targeting cancer stem cells. J Biomol Screen 2012; 17(9): 1231-42.
[8]
Desoize B, Jardillier J. Multicellular resistance: A paradigm for clinical resistance? Crit Rev Oncol Hematol 2000; 36(2-3): 193-207.
[9]
Friedrich J, Seidel C, Ebner R, Kunz-Schughart LA. Spheroid-based drug screen: considerations and practical approach. Nat Protoc 2009; 4(3): 309-24.
[10]
Debnath J, Brugge JS. Modelling glandular epithelial cancers in three-dimensional cultures. Nat Rev Cancer 2005; 5(9): 675-88.
[11]
Lee GY, Kenny PA, Lee EH, Bissell MJ. Three-dimensional culture models of normal and malignant breast epithelial cells. Nat Methods 2007; 4(4): 359-65.
[12]
Dolznig H, Walzl A, Kramer N, Rosner M, Garin-Chesa P, Hengstschläger M. Organotypic spheroid cultures to study tumor–stroma interaction during cancer development. Drug Discov Today Dis Models 2011; 8: 113-9.
[13]
Sharma R, Greenhough S, Medine CN, Hay DC. Three-dimensional culture of human embryonic stem cell derived hepatic endoderm and its role in bioartificial liver construction. J Biomed Biotechnol 2010; 2010: 236147.
[14]
Mehta G, Hsiao AY, Ingram M, Luker GD, Takayama S. Opportunities and challenges for use of tumor spheroids as models to test drug delivery and efficacy. J Control Release 2012; 164(2): 192-204.
[15]
Breslin S, O’Driscoll L. Three-dimensional cell culture: the missing link in drug discovery. Drug Discov Today 2013; 18(5-6): 240-9.
[16]
Kelm JM, Fussenegger M. Microscale tissue engineering using gravity-enforced cell assembly. Trends Biotechnol 2004; 22(4): 195-202.
[17]
Shekhar MPV. Drug resistance: challenges to effective therapy. Curr Cancer Drug Targets 2011; 11(5): 613-23.
[18]
Lin RZ, Chang HY. Recent advances in three-dimensional multicellular spheroid culture for biomedical research. Biotechnol J 2008; 3(9-10): 1172-84.
[19]
Florczyk SJ, Wang K, Jana S, et al. Porous chitosan-hyaluronic acid scaffolds as a mimic of glioblastoma microenvironment ECM. Biomaterials 2013; 34(38): 10143-50.
[20]
Hirschhaeuser F, Menne H, Dittfeld C, West J, Mueller-Klieser W, Kunz-Schughart LA. Multicellular tumor spheroids: An underestimated tool is catching up again. J Biotechnol 2010; 148(1): 3-15.
[21]
Kelm JM, Timmins NE, Brown CJ, Fussenegger M, Nielsen LK. Method for generation of homogeneous multicellular tumor spheroids applicable to a wide variety of cell types. Biotechnol Bioeng 2003; 83(2): 173-80.
[22]
Curcio E, Salerno S, Barbieri G, De Bartolo L, Drioli E, Bader A. Mass transfer and metabolic reactions in hepatocyte spheroids cultured in rotating wall gas-permeable membrane system. Biomaterials 2007; 28(36): 5487-97.
[23]
Friedrich J, Seidel C, Ebner R, Kunz-Schughart LA. Spheroid-based drug screen: considerations and practical approach. Nat Protoc 2009; 4(3): 309-24.
[24]
Ivascu A, Kubbies M. Rapid generation of single-tumor spheroids for high-throughput cell function and toxicity analysis. J Biomol Screen 2006; 11(8): 922-32.
[25]
Vinci M, Gowan S, Boxall F, et al. Advances in establishment and analysis of three-dimensional tumor spheroid-based functional assays for target validation and drug evaluation. BMC Biol 2012; 10: 29-9.
[26]
Thoma CR, Zimmermann M, Agarkova I, Kelm JM, Krek W. 3D cell culture systems modeling tumor growth determinants in cancer target discovery. Adv Drug Deliv Rev 2014; 69-70: 29-41.
[27]
Sasaki T, Yamamoto M, Yamaguchi T, Sugiyama S. Development of multicellular spheroids of HeLa cells cocultured with fibroblasts and their response to X-irradiation. Cancer Res 1984; 44(1): 345-51.
[28]
Hsiao AY, Torisawa YS, Tung YC, et al. Microfluidic system for formation of PC-3 prostate cancer co-culture spheroids. Biomaterials 2009; 30(16): 3020-7.
[29]
Frieboes HB, Zheng X, Sun CH, Tromberg B, Gatenby R, Cristini V. An integrated computational/experimental model of tumor invasion. Cancer Res 2006; 66(3): 1597-604.
[30]
Dangles-Marie V, Richon S, El-Behi M, et al. A three-dimensional tumor cell defect in activating autologous CTLs is associated with inefficient antigen presentation correlated with heat shock protein-70 down-regulation. Cancer Res 2003; 63(13): 3682-7.
[31]
Dangles V, Validire P, Wertheimer M, et al. Impact of human bladder cancer cell architecture on autologous T-lymphocyte activation. Int J Cancer 2002; 98(1): 51-6.
[32]
Hirschhaeuser F, Menne H, Dittfeld C, West J, Mueller-Klieser W, Kunz-Schughart LA. Multicellular tumor spheroids: An underestimated tool is catching up again. J Biotechnol 2010; 148(1): 3-15.
[33]
Nakazawa K, Izumi Y, Mori R. Morphological and functional studies of rat hepatocytes on a hydrophobic or hydrophilic polydimethylsiloxane surface. Acta Biomater 2009; 5(2): 613-20.
[34]
Shi Y, Ma J, Zhang X, Li H, Jiang L, Qin J. Hypoxia combined with spheroid culture improves cartilage specific function in chondrocytes. Integr Biol 2015; 7(3): 289-97.
[35]
Lei KF, Chang C-H, Chen M-J. Paper/PMMA Hybrid 3D Cell Culture Microfluidic Platform for the Study of Cellular Crosstalk. ACS Appl Mater Interfaces 2017; 9(15): 13092-101.
[36]
Gottwald E, Giselbrecht S, Augspurger C, et al. A chip-based platform for the in vitro generation of tissues in three-dimensional organization. Lab Chip 2007; 7(6): 777-85.
[37]
Ota H, Yamamoto R, Deguchi K, et al. Three-dimensional spheroid-forming lab-on-a-chip using micro-rotational flow. Sens Actuators B Chem 2010; 147: 359-65.
[38]
Velasco D, Tumarkin E, Kumacheva E. Microfluidic encapsulation of cells in polymer microgels. Small 2012; 8(11): 1633-42.
[39]
Zhang W, Zhao S, Rao W, et al. A novel core–shell microcapsule for encapsulation and 3D culture of embryonic stem cells. J Mater Chem B Mater Biol Med 2013; 2013(7): 1002-9.
[40]
Sakai S, Ito S, Inagaki H, et al. Cell-enclosing gelatin-based microcapsule production for tissue engineering using a microfluidic flow-focusing system. Biomicrofluidics 2011; 5(1): 13402.
[41]
Wang Y, Wang J. Mixed hydrogel bead-based tumor spheroid formation and anticancer drug testing. Analyst (Lond) 2014; 139(10): 2449-58.
[42]
Yoon S, Kim JA, Lee SH, Kim M, Park TH. Droplet-based microfluidic system to form and separate multicellular spheroids using magnetic nanoparticles. Lab Chip 2013; 13(8): 1522-8.
[43]
Alessandri K, Sarangi BR, Gurchenkov VV, et al. Cellular capsules as a tool for multicellular spheroid production and for investigating the mechanics of tumor progression in vitro. Proc Natl Acad Sci USA 2013; 110(37): 14843-8.
[44]
Zhang X, Wang W, Yu W, et al. Development of an in vitro multicellular tumor spheroid model using microencapsulation and its application in anticancer drug screening and testing. Biotechnol Prog 2005; 21(4): 1289-96.
[45]
Sakai S, Inamoto K, Liu Y, Tanaka S, Arii S, Taya M. Multicellular tumor spheroid formation in duplex microcapsules for analysis of chemosensitivity. Cancer Sci 2012; 103(3): 549-54.
[46]
Sakai S, Ito S, Kawakami K. Calcium alginate microcapsules with spherical liquid cores templated by gelatin microparticles for mass production of multicellular spheroids. Acta Biomater 2010; 6(8): 3132-7.
[47]
Toh Y-C, Zhang C, Zhang J, et al. A novel 3D mammalian cell perfusion-culture system in microfluidic channels. Lab Chip 2007; 7(3): 302-9.
[48]
Pickl M, Ries CH. Comparison of 3D and 2D tumor models reveals enhanced HER2 activation in 3D associated with an increased response to trastuzumab. Oncogene 2009; 28(3): 461-8.
[49]
Loessner D, Stok KS, Lutolf MP, Hutmacher DW, Clements JA, Rizzi SC. Bioengineered 3D platform to explore cell-ECM interactions and drug resistance of epithelial ovarian cancer cells. Biomaterials 2010; 31(32): 8494-506.
[50]
Chitcholtan K, Sykes PH, Evans JJ. The resistance of intracellular mediators to doxorubicin and cisplatin are distinct in 3D and 2D endometrial cancer. J Transl Med 2012; 10: 38.
[51]
Morizane A, Doi D, Kikuchi T, Nishimura K, Takahashi J. Small-molecule inhibitors of bone morphogenic protein and activin/nodal signals promote highly efficient neural induction from human pluripotent stem cells. J Neurosci Res 2011; 89(2): 117-26.
[52]
Wan X, Li Z, Ye H, Cui Z. Three-dimensional perfused tumour spheroid model for anti-cancer drug screening. Biotechnol Lett 2016; 38(8): 1389-95.
[53]
Dhiman HK, Ray AR, Panda AK. Three-dimensional chitosan scaffold-based MCF-7 cell culture for the determination of the cytotoxicity of tamoxifen. Biomaterials 2005; 26(9): 979-86.
[54]
Walker DM, Boey G, McDonald LA. The pathology of oral cancer. Pathology 2003; 35(5): 376-83.
[55]
Tung Y-C, Hsiao AY, Allen SG, Torisawa YS, Ho M, Takayama S. High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array. Analyst (Lond) 2011; 136(3): 473-8.
[56]
Vaupel P, Mayer A. Hypoxia and anemia: effects on tumor biology and treatment resistance. Transfus Clin Biol 2005; 12(1): 5-10.
[57]
Trédan O, Galmarini CM, Patel K, Tannock IF. Drug resistance and the solid tumor microenvironment. J Natl Cancer Inst 2007; 99(19): 1441-54.
[58]
Yip D, Cho CH. A multicellular 3D heterospheroid model of liver tumor and stromal cells in collagen gel for anti-cancer drug testing. Biochem Biophys Res Commun 2013; 433(3): 327-32.
[59]
Edmondson R, Broglie JJ, Adcock AF, Yang L. Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors. Assay Drug Dev Technol 2014; 12(4): 207-18.
[60]
Crystal AS, Shaw AT, Sequist LV, et al. Patient-derived models of acquired resistance can identify effective drug combinations for cancer. Science 2014; 346(6216): 1480-6.
[61]
Kondo J, Endo H, Okuyama H, et al. Retaining cell-cell contact enables preparation and culture of spheroids composed of pure primary cancer cells from colorectal cancer. Proc Natl Acad Sci USA 2011; 108(15): 6235-40.
[62]
Tashiro T, Okuyama H, Endo H, et al. In vivo and ex vivo cetuximab sensitivity assay using three-dimensional primary culture system to stratify KRAS mutant colorectal cancer. PLoS One 2017; 12(3): e0174151.
[63]
Kiyohara Y, Yoshino K, Kubota S, et al. Drug screening and grouping by sensitivity with a panel of primary cultured cancer spheroids derived from endometrial cancer. Cancer Sci 2016; 107(4): 452-60.
[64]
Yamaki T, Suenaga Y, Iuchi T, et al. Temozolomide suppresses MYC via activation of TAp63 to inhibit progression of human glioblastoma. Sci Rep 2013; 3: 1160.
[65]
Hong IS, Lee HY, Nam JS. Cancer stem cells: the ‘Achilles heel’ of chemo-resistant tumors. Recent Patents Anticancer Drug Discov 2015; 10(1): 2-22.
[66]
Qiu H, Fang X, Luo Q, Ouyang G. Cancer stem cells: A potential target for cancer therapy. Cell Mol Life Sci 2015; 72(18): 3411-24.
[67]
Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001; 414(6859): 105-11.
[68]
Dalerba P, Cho RW, Clarke MF. Cancer stem cells: models and concepts. Annu Rev Med 2007; 58: 267-84.
[69]
Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994; 367(6464): 645-8.
[70]
Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003; 100(7): 3983-8.
[71]
Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature 2004; 432(7015): 396-401.
[72]
Kim CF, Jackson EL, Woolfenden AE, et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 2005; 121(6): 823-35.
[73]
Xin L, Lawson DA, Witte ON. The Sca-1 cell surface marker enriches for a prostate-regenerating cell subpopulation that can initiate prostate tumorigenesis. Proc Natl Acad Sci USA 2005; 102(19): 6942-7.
[74]
Suetsugu A, Nagaki M, Aoki H, Motohashi T, Kunisada T, Moriwaki H. Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem Biophys Res Commun 2006; 351(4): 820-4.
[75]
Li C, Lee CJ, Simeone DM. Identification of human pancreatic cancer stem cells. Methods Mol Biol 2009; 568: 161-73.
[76]
Li C, Heidt DG, Dalerba P, et al. Identification of pancreatic cancer stem cells. Cancer Res 2007; 67(3): 1030-7.
[77]
Prince ME, Sivanandan R, Kaczorowski A, et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA 2007; 104(3): 973-8.
[78]
Alison MR, Lin WR, Lim SM, Nicholson LJ. Cancer stem cells: in the line of fire. Cancer Treat Rev 2012; 38(6): 589-98.
[79]
Leon G, MacDonagh L, Finn SP, Cuffe S, Barr MP. Cancer stem cells in drug resistant lung cancer: Targeting cell surface markers and signaling pathways. Pharmacol Ther 2015.
[80]
Kise K, Kinugasa-Katayama Y, Takakura N. Tumor microenvironment for cancer stem cells. Adv Drug Deliv Rev 2015.
[81]
Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res 2003; 63(18): 5821-8.
[82]
Ponti D, Costa A, Zaffaroni N, et al. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 2005; 65(13): 5506-11.
[83]
Qiu X, Wang Z, Li Y, Miao Y, Ren Y, Luan Y. Characterization of sphere-forming cells with stem-like properties from the small cell lung cancer cell line H446. Cancer Lett 2012; 323(2): 161-70.
[84]
Yin BB, Wu SJ, Zong HJ, Ma BJ, Cai D. Preliminary screening and identification of stem cell-like sphere clones in a gallbladder cancer cell line GBC-SD. J Zhejiang Univ Sci B 2011; 12(4): 256-63.
[85]
Ghods AJ, Irvin D, Liu G, et al. Spheres isolated from 9L gliosarcoma rat cell line possess chemoresistant and aggressive cancer stem-like cells. Stem Cells 2007; 25(7): 1645-53.
[86]
Izumiya M, Kabashima A, Higuchi H, et al. Chemoresistance is associated with cancer stem cell-like properties and epithelial-to-mesenchymal transition in pancreatic cancer cells. Anticancer Res 2012; 32(9): 3847-53.
[87]
Li YF, Xiao B, Tu SF, Wang YY, Zhang XL. Cultivation and identification of colon cancer stem cell-derived spheres from the Colo205 cell line. Braz J Med Biol Res 2012; 45(3): 197-204.
[88]
Ma B, Lei X, Guan Y, et al. Maintenance of retinal cancer stem cell-like properties through long-term serum-free culture from human retinoblastoma. Oncol Rep 2011; 26(1): 135-43.
[89]
Tan H, Gao X, Sun J, Xiao C, Hu X. Double stimulus-induced stem cell aggregation during differentiation on a biopolymer hydrogel substrate. Chem Commun (Camb) 2013; 49(98): 11554-6.
[90]
Bernard AB, Lin CC, Anseth KS. A microwell cell culture platform for the aggregation of pancreatic β-cells. Tissue Eng Part C Methods 2012; 18(8): 583-92.
[91]
Mohr JC, de Pablo JJ, Palecek SP. 3-D microwell culture of human embryonic stem cells. Biomaterials 2006; 27(36): 6032-42.
[92]
Chiou SH, Wang ML, Chou YT, et al. Coexpression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation. Cancer Res 2010; 70(24): 10433-44.
[93]
Gou S, Liu T, Wang C, et al. Establishment of clonal colony-forming assay for propagation of pancreatic cancer cells with stem cell properties. Pancreas 2007; 34(4): 429-35.
[94]
Ye J, Wu D, Wu P, Chen Z, Huang J. The cancer stem cell niche: cross talk between cancer stem cells and their microenvironment. Tumour Biol 2014; 35(5): 3945-51.
[95]
Yi SY, Hao YB, Nan KJ, Fan TL. Cancer stem cells niche: A target for novel cancer therapeutics. Cancer Treat Rev 2013; 39(3): 290-6.
[96]
Jiang D, Liang J, Noble PW. Hyaluronan in tissue injury and repair. Annu Rev Cell Dev Biol 2007; 23: 435-61.
[97]
Williams K, Motiani K, Giridhar PV, Kasper S. CD44 integrates signaling in normal stem cell, cancer stem cell and (pre)metastatic niches. Exp Biol Med (Maywood) 2013; 238(3): 324-38.
[98]
Endo K, Terada T. Protein expression of CD44 (standard and variant isoforms) in hepatocellular carcinoma: relationships with tumor grade, clinicopathologic parameters, p53 expression, and patient survival. J Hepatol 2000; 32(1): 78-84.
[99]
Bourguignon LY. Hyaluronan-CD44 interaction promotes microRNA signaling and RhoGTPase activation leading to tumor progression. Small GTPases 2012; 3(1): 53-9.
[100]
Bourguignon LY, Shiina M, Li JJ. Hyaluronan-CD44 interaction promotes oncogenic signaling, microRNA functions, chemoresistance, and radiation resistance in cancer stem cells leading to tumor progression. Adv Cancer Res 2014; 123: 255-75.
[101]
Lee IC, Chuang CC, Wu YC. Niche Mimicking for Selection and Enrichment of Liver Cancer Stem Cells by Hyaluronic Acid-Based Multilayer Films. ACS Appl Mater Interfaces 2015; 7(40): 22188-95.
[102]
Shervington A, Lu C. Expression of multidrug resistance genes in normal and cancer stem cells. Cancer Invest 2008; 26(5): 535-42.
[103]
Zhou S, Schuetz JD, Bunting KD, et al. The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med 2001; 7(9): 1028-34.
[104]
Mueller MT, Hermann PC, Witthauer J, et al. Combined targeted treatment to eliminate tumorigenic cancer stem cells in human pancreatic cancer. Gastroenterology 2009; 137(3): 1102-13.
[105]
Dylla SJ, Beviglia L, Park IK, et al. Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS One 2008; 3(6): e2428.
[106]
Ma S, Lee TK, Zheng BJ, Chan KW, Guan XY. CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene 2008; 27(12): 1749-58.
[107]
Levina V, Marrangoni AM, DeMarco R, Gorelik E, Lokshin AE. Drug-selected human lung cancer stem cells: cytokine network, tumorigenic and metastatic properties. PLoS One 2008; 3(8): e3077.
[108]
Dano K. Active outward transport of daunomycin in resistant Ehrlich ascites tumor cells. Biochim Biophys Acta 1973; 323(3): 466-83.
[109]
Li Y, Kong D, Ahmad A, Bao B, Sarkar FH. Pancreatic cancer stem cells: emerging target for designing novel therapy. Cancer Lett 2013; 338(1): 94-100.
[110]
Hong SP, Wen J, Bang S, Park S, Song SY. CD44-positive cells are responsible for gemcitabine resistance in pancreatic cancer cells. Int J Cancer 2009; 125(10): 2323-31.
[111]
Gupta PB, Onder TT, Jiang G, et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 2009; 138(4): 645-59.
[112]
Zhang GN, Liang Y, Zhou LJ, et al. Combination of salinomycin and gemcitabine eliminates pancreatic cancer cells. Cancer Lett 2011; 313(2): 137-44.
[113]
Hong J, Edel JB, deMello AJ. Micro- and nanofluidic systems for high-throughput biological screening. Drug Discov Today 2009; 14(3-4): 134-46.
[114]
Zhao L, Wang Z, Fan S, et al. Chemotherapy resistance research of lung cancer based on micro-fluidic chip system with flow medium. Biomed Microdevices 2010; 12(2): 325-32.
[115]
Dittrich PS, Manz A. Lab-on-a-chip: microfluidics in drug discovery. Nat Rev Drug Discov 2006; 5(3): 210-8.
[116]
Wlodkowic D, Cooper JM. Tumors on chips: oncology meets microfluidics. Curr Opin Chem Biol 2010; 14(5): 556-67.
[117]
Ziółkowska K, Stelmachowska A, Kwapiszewski R, Chudy M, Dybko A, Brzózka Z. Long-term three-dimensional cell culture and anticancer drug activity evaluation in a microfluidic chip. Biosens Bioelectron 2013; 40(1): 68-74.
[118]
Xu Z, Gao Y, Hao Y, et al. Application of a microfluidic chip-based 3D co-culture to test drug sensitivity for individualized treatment of lung cancer. Biomaterials 2013; 34(16): 4109-17.
[119]
Toh YC, Zhang C, Zhang J, et al. A novel 3D mammalian cell perfusion-culture system in microfluidic channels. Lab Chip 2007; 7(3): 302-9.
[120]
Faley SL, Copland M, Wlodkowic D, et al. Microfluidic single cell arrays to interrogate signalling dynamics of individual, patient-derived hematopoietic stem cells. Lab Chip 2009; 9(18): 2659-64.
[121]
Chen Y, Gao D, Liu H, Lin S, Jiang Y. Drug cytotoxicity and signaling pathway analysis with three-dimensional tumor spheroids in a microwell-based microfluidic chip for drug screening. Anal Chim Acta 2015; 898: 85-92.
[122]
Dereli-Korkut Z, Akaydin HD, Ahmed AH, Jiang X, Wang S. Three dimensional microfluidic cell arrays for ex vivo drug screening with mimicked vascular flow. Anal Chem 2014; 86(6): 2997-3004.
[123]
Skardal A, Devarasetty M, Forsythe S, Atala A, Soker S. A reductionist metastasis-on-a-chip platform for in vitro tumor progression modeling and drug screening. Biotechnol Bioeng 2016; 113(9): 2020-32.
[124]
Sung JH, Shuler ML. A micro cell culture analog (microCCA) with 3-D hydrogel culture of multiple cell lines to assess metabolism-dependent cytotoxicity of anti-cancer drugs. Lab Chip 2009; 9(10): 1385-94.
[125]
Sung JH, Kam C, Shuler ML. A microfluidic device for a pharmacokinetic-pharmacodynamic (PK-PD) model on a chip. Lab Chip 2010; 10(4): 446-55.
[126]
Yu M, Bardia A, Aceto N, et al. Cancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. Science 2014; 345(6193): 216-20.
[127]
Praharaj PP, Bhutia SK, Nagrath S, Bitting RL, Deep G. Circulating tumor cell-derived organoids: Current challenges and promises in medical research and precision medicine. Biochim Biophys Acta Rev Cancer 2018; 1869(2): 117-27.
[128]
Azizi E, Nagrath S, Kozminsky M, Wicha MS. Cancer Stem Cells and Circulating Tumor Cells: Molecular Markers, Isolation Techniques, and Clinical Implications. In: Cote RJ, Datar RH, ed.^eds., Circulating Tumor Cells. Springer New York: New York, NY, 2016; pp. 75-97.
[129]
Miller MC, Doyle GV, Terstappen LWMM. Significance of Circulating Tumor Cells Detected by the CellSearch System in Patients with Metastatic Breast Colorectal and Prostate Cancer. J Oncol 2010; 2010: 617421.
[130]
Stott SL, Hsu C-H, Tsukrov DI, et al. Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. Proc Natl Acad Sci USA 2010; 107(43): 18392-7.
[131]
Saucedo-Zeni N, Mewes S, Niestroj R, et al. A novel method for the in vivo isolation of circulating tumor cells from peripheral blood of cancer patients using a functionalized and structured medical wire. Int J Oncol 2012; 41(4): 1241-50.
[132]
Hoshino K, Huang Y-Y, Lane N, et al. Microchip-based immunomagnetic detection of circulating tumor cells. Lab Chip 2011; 11(20): 3449-57.
[133]
Daniel VC, Marchionni L, Hierman JS, et al. A primary xenograft model of small-cell lung cancer reveals irreversible changes in gene expression imposed by culture in vitro. Cancer Res 2009; 69(8): 3364-73.
[134]
Meijer TG, Naipal KAT, Jager A, van Gent DC. Ex vivo tumor culture systems for functional drug testing and therapy response prediction. Future Sci OA 2017; 3(2): FSO190.
[135]
Astolfi M, Péant B, Lateef MA, et al. Micro-dissected tumor tissues on chip: An ex vivo method for drug testing and personalized therapy. Lab Chip 2016; 16(2): 312-25.
[136]
Ranga A, Gjorevski N, Lutolf MP. Drug discovery through stem cell-based organoid models. Adv Drug Deliv Rev 2014; 69-70: 19-28.
[137]
Sato T, Vries RG, Snippert HJ, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 2009; 459(7244): 262-5.
[138]
Sato T, Stange DE, Ferrante M, et al. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology 2011; 141(5): 1762-72.
[139]
Drost J, Clevers H. Organoids in cancer research. Nat Rev Cancer 2018; 18(7): 407-18.
[140]
Sachs N, Clevers H. Organoid cultures for the analysis of cancer phenotypes. Curr Opin Genet Dev 2014; 24: 68-73.
[141]
Mazzocchi AR, Rajan SAP, Votanopoulos KI, Hall AR, Skardal A. In vitro patient-derived 3D mesothelioma tumor organoids facilitate patient-centric therapeutic screening. Sci Rep 2018; 8(1): 2886.
[142]
Vlachogiannis G, Hedayat S, Vatsiou A, et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science 2018; 359(6378): 920-6.
[143]
Skardal A, Shupe T, Atala A. Organoid-on-a-chip and body-on-a-chip systems for drug screening and disease modeling. Drug Discov Today 2016; 21(9): 1399-411.

Rights & Permissions Print Cite
Article Metrics
60
8
© 2024 Bentham Science Publishers | Privacy Policy