Skip to main content
SpringerLink
Log in

Microfluidics and Future of Cancer Diagnostics

  • Chapter
  • First Online:
Ex Vivo Engineering of the Tumor Microenvironment

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

The interaction of tumor cells with their surrounding stroma is dynamic and complex throughout the metastatic growth. Additionally, these interactions play a major role in therapeutic outcome. Here we first discuss the major players in the tumor microenvironment, including the immune environment. Next, we discuss in vivo and ex vivo approaches for studying different stages of the metastatic cascade. Among these approaches, we focus on microfluidic devices that have progressed rapidly in the past decade. Finally, we discuss the application of microfluidic assays in determining appropriate therapeutic approaches for specific patients to promote efforts in the field of personalized medicine.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Turley SJ, Cremasco V, Astarita JL (2015) Immunological hallmarks of stromal cells in the tumour microenvironment. Nat Rev Immunol 15:669–682

    Article  CAS  PubMed  Google Scholar 

  2. Adotevi O, Pere H, Ravel P, Haicheur N, Badoual C, Merillon N, Medioni J, Peyrard S, Roncelin S, Verkarre V, Mejean A, Fridman WH, Oudard S, Tartour E (2010) A decrease of regulatory T cells correlates with overall survival after sunitinib-based antiangiogenic therapy in metastatic renal cancer patients. J Immunother 33:991–998

    Article  CAS  PubMed  Google Scholar 

  3. Ko JS, Zea AH, Rini BI, Ireland JL, Elson P, Cohen P, Golshayan A, Rayman PA, Wood L, Garcia J, Dreicer R, Bukowski R, Finke JH (2009) Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res 15:2148–2157

    Article  CAS  PubMed  Google Scholar 

  4. Mueller MM, Fusenig NE (2004) Friends or foes – bipolar effects of the tumour stroma in cancer. Nat Rev Cancer 4:839–849

    Article  CAS  PubMed  Google Scholar 

  5. Joyce JA, Pollard JW (2009) Microenvironmental regulation of metastasis. Nat Rev Cancer 9:239–252

    Article  CAS  PubMed  Google Scholar 

  6. Nakasone ES, Askautrud HA, Kees T, Park JH, Plaks V, Ewald AJ, Fein M, Rasch MG, Tan YX, Qiu J, Park J, Sinha P, Bissell MJ, Frengen E, Werb Z, Egeblad M (2012) Imaging tumor-stroma interactions during chemotherapy reveals contributions of the microenvironment to resistance. Cancer Cell 21:488–503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Polyak K, Haviv I, Campbell IG (2009) Co-evolution of tumor cells and their microenvironment. Trends Genet 25:30–38

    Article  CAS  PubMed  Google Scholar 

  8. Chen DS, Mellman I (2013) Oncology meets immunology: the cancer-immunity cycle. Immunity 39:1–10

    Article  PubMed  Google Scholar 

  9. Pivarcsi A, Muller A, Hippe A, Rieker J, van Lierop A, Steinhoff M, Seeliger S, Kubitza R, Pippirs U, Meller S, Gerber PA, Liersch R, Buenemann E, Sonkoly E, Wiesner U, Hoffmann TK, Schneider L, Piekorz R, Enderlein E, Reifenberger J, Rohr UP, Haas R, Boukamp P, Haase I, Nurnberg B, Ruzicka T, Zlotnik A, Homey B (2007) Tumor immune escape by the loss of homeostatic chemokine expression. Proc Natl Acad Sci U S A 104:19055–19060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Herbst RS, Soria J-C, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HEK, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS (2014) Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515(7528):563–567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Powles T, Eder JP, Fine GD, Braiteh FS, Loriot Y, Cruz C, Bellmunt J, Burris HA, Petrylak DP, S-l T, Shen X, Boyd Z, Hegde PS, Chen DS, Vogelzang NJ (2014) MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 515(7528):558–562

    Article  CAS  PubMed  Google Scholar 

  12. Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJM, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, West AN, Carmona M, Kivork C, Seja E, Cherry G, Gutierrez AJ, Grogan TR, Mateus C, Tomasic G, Glaspy JA, Emerson RO, Robins H, Pierce RH, Elashoff DA, Robert C, Ribas A (2014) PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515(7528):568–571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Butler TP, Grantham FH, Gullino PM (1975) Bulk transfer of fluid in the interstitial compartment of mammary tumors. Cancer Res 35:3084–3088

    CAS  PubMed  Google Scholar 

  14. Fukumura D, Jain RK (2007) Tumor microenvironment abnormalities: causes, consequences, and strategies to normalize. J Cell Biochem 101:937–949

    Article  CAS  PubMed  Google Scholar 

  15. Swartz MA, Lund AW (2012) Lymphatic and interstitial flow in the tumour microenvironment: linking mechanobiology with immunity. Nat Rev Cancer 12:210–219

    Article  CAS  PubMed  Google Scholar 

  16. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  CAS  PubMed  Google Scholar 

  17. DuFort CC, Paszek MJ, Weaver VM (2011) Balancing forces: architectural control of mechanotransduction. Nat Rev Mol Cell Biol 12:308–319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Xu R, Boudreau A, Bissell MJ (2009) Tissue architecture and function: dynamic reciprocity via extra- and intra-cellular matrices. Cancer Metastasis Rev 28:167–176

    Article  PubMed  PubMed Central  Google Scholar 

  19. Heldin CH, Rubin K, Pietras K, Ostman A (2004) High interstitial fluid pressure – an obstacle in cancer therapy. Nat Rev Cancer 4:806–813

    Article  CAS  PubMed  Google Scholar 

  20. Wiig H (1990) Evaluation of methodologies for measurement of interstitial fluid pressure (Pi): physiological implications of recent Pi data. Crit Rev Biomed Eng 18:27–54

    CAS  PubMed  Google Scholar 

  21. Jain RK (2008) Lessons from multidisciplinary translational trials on anti-angiogenic therapy of cancer. Nat Rev Cancer 8:309–316

    Article  CAS  PubMed  Google Scholar 

  22. Flessner MF, Choi J, Credit K, Deverkadra R, Henderson K (2005) Resistance of tumor interstitial pressure to the penetration of intraperitoneally delivered antibodies into metastatic ovarian tumors. Clin Cancer Res 11:3117–3125

    Article  CAS  PubMed  Google Scholar 

  23. Wiig H, Tveit E, Hultborn R, Reed RK, Weiss L (1982) Interstitial fluid pressure in DMBA-induced rat mammary tumours. Scand J Clin Lab Invest 42:159–164

    Article  CAS  PubMed  Google Scholar 

  24. Raju B, Haug SR, Ibrahim SO, Heyeraas KJ (2008) High interstitial fluid pressure in rat tongue cancer is related to increased lymph vessel area, tumor size, invasiveness and decreased body weight. J Oral Pathol Med 37:137–144

    Article  PubMed  Google Scholar 

  25. Pedersen JA, Boschetti F, Swartz MA (2007) Effects of extracellular fiber architecture on cell membrane shear stress in a 3D fibrous matrix. J Biomech 40:1484–1492

    Article  PubMed  Google Scholar 

  26. Albini A, Sporn MB (2007) The tumour microenvironment as a target for chemoprevention. Nat Rev Cancer 7:139–147

    Article  CAS  PubMed  Google Scholar 

  27. Fang X, Sittadjody S, Gyabaah K, Opara EC, Balaji KC (2013) Novel 3D co-culture model for epithelial-stromal cells interaction in prostate cancer. PLoS One 8, e75187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Gurski LA, Jha AK, Zhang C, Jia X, Farach-Carson MC (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 

  29. Carvalho MR, Lima D, Reis RL, Correlo VM, Oliveira JM (2015) Evaluating biomaterial- and microfluidic-based 3D tumor models. Trends Biotechnol 33:667–678

    Article  CAS  PubMed  Google Scholar 

  30. Cheema U, Brown RA, Alp B, MacRobert AJ (2008) Spatially defined oxygen gradients and vascular endothelial growth factor expression in an engineered 3D cell model. Cell Mol Life Sci 65:177–186

    Article  CAS  PubMed  Google Scholar 

  31. Kenny PA, Bissell MJ (2007) Targeting TACE-dependent EGFR ligand shedding in breast cancer. J Clin Invest 117:337–345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ridky TW, Chow JM, Wong DJ, Khavari PA (2010) Invasive three-dimensional organotypic neoplasia from multiple normal human epithelia. Nat Med 16:1450–1455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wozniak MA, Modzelewska K, Kwong L, Keely PJ (2004) Focal adhesion regulation of cell behavior. Biochim Biophys Acta 1692:103–119

    Article  CAS  PubMed  Google Scholar 

  34. Rimann M, Graf-Hausner U (2012) Synthetic 3D multicellular systems for drug development. Curr Opin Biotechnol 23:803–809

    Article  CAS  PubMed  Google Scholar 

  35. Orlandi P, Barbara C, Bocci G, Fioravanti A, Di Paolo A, Del Tacca M, Danesi R (2005) Idarubicin and idarubicinol effects on breast cancer multicellular spheroids. J Chemother 17:663–667

    Article  CAS  PubMed  Google Scholar 

  36. Tung YC, Hsiao AY, Allen SG, Torisawa YS, Ho M, Takayama S (2011) High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array. Analyst 136:473–478

    Article  CAS  PubMed  Google Scholar 

  37. Mano JF (2015) Designing biomaterials for tissue engineering based on the deconstruction of the native cellular environment. Mater Lett 141:198–202

    Article  CAS  Google Scholar 

  38. Goodman TT, Ng CP, Pun SH (2008) 3-D tissue culture systems for the evaluation and optimization of nanoparticle-based drug carriers. Bioconjug Chem 19:1951–1959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Li Z, Wang Y, Dong S, Ge C, Xiao Y, Li R, Ma X, Xue Y, Zhang Q, Lv J, Tan Q, Zhu Z, Song X, Tan J (2014) Association of CXCR1 and 2 expressions with gastric cancer metastasis in ex vivo and tumor cell invasion in vitro. Cytokine 69:6–13

    Article  CAS  PubMed  Google Scholar 

  40. Rangarajan A, Weinberg RA (2003) Comparative biology of mouse versus human cells: modelling human cancer in mice. Nat Rev Cancer 3:952–959

    Article  CAS  PubMed  Google Scholar 

  41. Yamada KM, Cukierman E (2007) Modeling tissue morphogenesis and cancer in 3D. Cell 130:601–610

    Article  CAS  PubMed  Google Scholar 

  42. Hwu D, Boutrus S, Greiner C, DiMeo T, Kuperwasser C, Georgakoudi I (2011) Assessment of the role of circulating breast cancer cells in tumor formation and metastatic potential using in vivo flow cytometry. J Biomed Opt 16:040501

    Article  PubMed  Google Scholar 

  43. Sahai E (2007) Illuminating the metastatic process. Nat Rev Cancer 7:737–749

    Article  CAS  PubMed  Google Scholar 

  44. Wyckoff JB, Wang Y, Lin EY, Li JF, Goswami S, Stanley ER, Segall JE, Pollard JW, Condeelis J (2007) Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Res 67:2649–2656

    Article  CAS  PubMed  Google Scholar 

  45. Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2:563–572

    Article  CAS  PubMed  Google Scholar 

  46. Boussommier-Calleja A, Li R, Chen MB, Wong SC, Kamm RD (2016) Microfluidics: a new tool for modeling cancer-immune interactions. Trends Cancer 2:6–19

    Article  PubMed  Google Scholar 

  47. Jeon JS, Zervantonakis IK, Chung S, Kamm RD, Charest JL (2013) In vitro model of tumor cell extravasation. PLoS One 8, e56910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Lee H, Park W, Ryu H, Jeon NL (2014) A microfluidic platform for quantitative analysis of cancer angiogenesis and intravasation. Biomicrofluidics 8:054102

    Article  PubMed  PubMed Central  Google Scholar 

  49. Riahi R, Yang YL, Kim H, Jiang L, Wong PK, Zohar Y (2014) A microfluidic model for organ-specific extravasation of circulating tumor cells. Biomicrofluidics 8:024103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Zervantonakis IK, Hughes-Alford SK, Charest JL, Condeelis JS, Gertler FB, Kamm RD (2012) Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function. Proc Natl Acad Sci U S A 109:13515–13520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Zhang Q, Liu T, Qin J (2012) A microfluidic-based device for study of transendothelial invasion of tumor aggregates in realtime. Lab Chip 12:2837–2842

    Article  CAS  PubMed  Google Scholar 

  52. Shin MK, Kim SK, Jung H (2011) Integration of intra- and extravasation in one cell-based microfluidic chip for the study of cancer metastasis. Lab Chip 11:3880–3887

    Article  CAS  PubMed  Google Scholar 

  53. Song JW, Cavnar SP, Walker AC, Luker KE, Gupta M, Tung YC, Luker GD, Takayama S (2009) Microfluidic endothelium for studying the intravascular adhesion of metastatic breast cancer cells. PLoS One 4, e5756

    Article  PubMed  PubMed Central  Google Scholar 

  54. Kim S, Lee H, Chung M, Jeon NL (2013) Engineering of functional, perfusable 3D microvascular networks on a chip. Lab Chip 13:1489–1500

    Article  CAS  PubMed  Google Scholar 

  55. Whisler JA, Chen MB, Kamm RD (2014) Control of perfusable microvascular network morphology using a multiculture microfluidic system. Tissue engineering Part C. Methods 20:543–552

    CAS  Google Scholar 

  56. Jeon JS, Bersini S, Whisler JA, Chen MB, Dubini G, Charest JL, Moretti M, Kamm RD (2014) Generation of 3D functional microvascular networks with human mesenchymal stem cells in microfluidic systems. Integr Biol 6:555–563

    Article  CAS  Google Scholar 

  57. Chen MB, Whisler JA, Jeon JS, Kamm RD (2013) Mechanisms of tumor cell extravasation in an in vitro microvascular network platform. Integr Biol 5:1262–1271

    Article  CAS  Google Scholar 

  58. Ehsan SM, Welch-Reardon KM, Waterman ML, Hughes CC, George SC (2014) A three-dimensional in vitro model of tumor cell intravasation. Integr Biol 6:603–610

    Article  CAS  Google Scholar 

  59. Ghajar CM, Peinado H, Mori H, Matei IR, Evason KJ, Brazier H, Almeida D, Koller A, Hajjar KA, Stainier DY, Chen EI, Lyden D, Bissell MJ (2013) The perivascular niche regulates breast tumour dormancy. Nat Cell Biol 15:807–817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kuo CT, Chiang CL, Chang CH, Liu HK, Huang GS, Huang RY, Lee H, Huang CS, Wo AM (2014) Modeling of cancer metastasis and drug resistance via biomimetic nano-cilia and microfluidics. Biomaterials 35:1562–1571

    Article  CAS  PubMed  Google Scholar 

  61. Kuo CT, Liu HK, Huang GS, Chang CH, Chen CL, Chen KC, Huang RY, Lin CH, Lee H, Huang CS, Wo AM (2014) A spatiotemporally defined in vitro microenvironment for controllable signal delivery and drug screening. Analyst 139:4846–4854

    Article  CAS  PubMed  Google Scholar 

  62. Bischel LL, Beebe DJ, Sung KE (2015) Microfluidic model of ductal carcinoma in situ with 3D, organotypic structure. BMC Cancer 15:12

    Article  PubMed  PubMed Central  Google Scholar 

  63. Sung KE, Yang N, Pehlke C, Keely PJ, Eliceiri KW, Friedl A, Beebe DJ (2011) Transition to invasion in breast cancer: a microfluidic in vitro model enables examination of spatial and temporal effects. Integr Biol 3:439–450

    Article  CAS  Google Scholar 

  64. Acosta MA, Jiang X, Huang PK, Cutler KB, Grant CS, Walker GM, Gamcsik MP (2014) A microfluidic device to study cancer metastasis under chronic and intermittent hypoxia. Biomicrofluidics 8:054117

    Article  PubMed  PubMed Central  Google Scholar 

  65. Pisano M, Triacca V, Barbee KA, Swartz MA (2015) An in vitro model of the tumor-lymphatic microenvironment with simultaneous transendothelial and luminal flows reveals mechanisms of flow enhanced invasion. Integr Biol 7:525–533

    Article  CAS  Google Scholar 

  66. Kim J, Bae S, An S, Park JK, Kim EM, Hwang SG, Kim WJ, Um HD (2014) Cooperative actions of p21WAF1 and p53 induce Slug protein degradation and suppress cell invasion. EMBO Rep 15:1062–1068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Bersini S, Jeon JS, Dubini G, Arrigoni C, Chung S, Charest JL, Moretti M, Kamm RD (2014) A microfluidic 3D in vitro model for specificity of breast cancer metastasis to bone. Biomaterials 35:2454–2461

    Article  CAS  PubMed  Google Scholar 

  68. Chaw KC, Manimaran M, Tay EH, Swaminathan S (2007) Multi-step microfluidic device for studying cancer metastasis. Lab Chip 7:1041–1047

    Article  CAS  PubMed  Google Scholar 

  69. Bersini S, Jeon JS, Moretti M, Kamm RD (2014) In vitro models of the metastatic cascade: from local invasion to extravasation. Drug Discov Today 19:735–742

    Article  CAS  PubMed  Google Scholar 

  70. Fidler IJ (2003) The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer 3:453–458

    Article  CAS  PubMed  Google Scholar 

  71. Fitzgerald DP, Palmieri D, Hua E, Hargrave E, Herring JM, Qian Y, Vega-Valle E, Weil RJ, Stark AM, Vortmeyer AO, Steeg PS (2008) Reactive glia are recruited by highly proliferative brain metastases of breast cancer and promote tumor cell colonization. Clin Exp Metastasis 25:799–810

    Article  PubMed  PubMed Central  Google Scholar 

  72. Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE (2010) Reconstituting organ-level lung functions on a chip. Science 328:1662–1668

    Article  CAS  PubMed  Google Scholar 

  73. Aref RA, Huang RJ, Weimian Y, Weng S, Thiery JP, Kamm RD (2013) Screening therapeutic EMT blocking agents. Integr Biol 5:381–389

    Article  CAS  Google Scholar 

  74. Zhu Z, Aref AR et al (2014) Inhibition of KRAS-driven tumorigenicity by interruption of an autocrine cytokine circuit. Cancer Discov 4:452–465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Barbie TU, Alexe G, Zhu Z, Aref AR, Hahn WC, Barbie DA, Gillanders WE (2014) IKKε induces a cytokine signaling network essential for tumorigenicity. J Clin Invest 124(12):5411–5423

    Article  PubMed  PubMed Central  Google Scholar 

  76. Hirt C, Papadimitropoulos A, Mele V, Muraro MG, Mengus C, Iezzi G, Terracciano L, Martin I, Spagnoli GC (2014) “In vitro” 3D models of tumor-immune system interaction. Adv Drug Deliv Rev 79–80:145–154

    Article  PubMed  Google Scholar 

  77. Tan L et al (2014) Overcoming FGFR-resistance with covalent inhibitors. Proc Natl Acad Sci U S A 109:11–45. Li Tan, Jun Wang, Junko Tanizaki, Zhifeng Huang, Amir R. Aref, Maria Rusan, Su-Jie Zhu, Yiyun Zhang, Dalia Ercan, Rachel G. Liao, Marzia Capelletti, Wenjun Zhou, Wooyoung Hur, NamDoo Kim, Taebo Sim, Suzanne Gaudet, David A. Barbie, Jing-Ruey Joanna Yeh, Cai-Hong Yun, Peter S. Hammerman, Moosa Mohammadi, Pasi A. Jänne, and Nathanael S. Gray Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors PNAS 2014 111 (45) E4869–E4877; published ahead of print October 27, 2014, doi:10.1073/pnas.1403438111.

  78. Swartz MA, Hirosue S, Hubbell JA (2012) Engineering approaches to immunotherapy. Sci Transl Med 4:148–149

    Article  Google Scholar 

  79. Hamid O, Robert C, Daud A, Hodi FS, Hwu W-J, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS, Dronca R, Gangadhar TC, Patnaik A, Zarour H, Joshua AM, Gergich K, Elassaiss-Schaap J, Algazi A, Mateus C, Boasberg P, Tumeh PC, Chmielowski B, Ebbinghaus SW, Li XN, Kang SP and Ribas A. N Engl J Med. 2013 Jul 11;369(2):134-44. doi:10.1056/NEJMoa1305133. Epub 2013 Jun 2.Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma.

  80. Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon R-A, Reed K, Burke MM, Caldwell A, Kronenberg SA, Agunwamba BU, Zhang X, Lowy I, Inzunza HD, Feely W, Horak CE, Hong Q, Korman AJ, Wigginton JM, Gupta A and Sznol M. N Engl J Med. 2013 Jul 11;369(2):122–33. doi:10.1056/NEJMoa1302369. Epub 2013 Jun 2.Nivolumab plus ipilimumab in advanced melanoma.

  81. Sharma P and Allison JP (2015) Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell. 161(2):205–14. doi:10.1016/j.cell.2015.03.030.

  82. Turcotte S, Rosenberg SA (2011) Immunotherapy for metastatic solid cancers. Adv Surg 45:341–360

    Article  PubMed  PubMed Central  Google Scholar 

  83. Bhatia SN, Ingber DE (2014) Microfluidic organs-on-chips. Nat Biotechnol 32:760–772

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Bioengineering, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK

    Samira Jamalian & Mohammad Jafarnejad

  2. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA

    Amir R. Aref

Authors
  1. Samira Jamalian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohammad Jafarnejad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Amir R. Aref
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Samira Jamalian or Amir R. Aref .

Editor information

Editors and Affiliations

  1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

    Amir R. Aref

  2. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

    David Barbie

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Jamalian, S., Jafarnejad, M., Aref, A.R. (2017). Microfluidics and Future of Cancer Diagnostics. In: Aref, A., Barbie, D. (eds) Ex Vivo Engineering of the Tumor Microenvironment. Cancer Drug Discovery and Development. Humana Press, Cham. https://doi.org/10.1007/978-3-319-45397-2_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-45397-2_4

  • Published:

  • Publisher Name: Humana Press, Cham

  • Print ISBN: 978-3-319-45395-8

  • Online ISBN: 978-3-319-45397-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation