Skip to main content
SpringerLink
Log in

Necrosis in the Tumor Microenvironment and Its Role in Cancer Recurrence

  • Chapter
  • First Online:
Tumor Microenvironment

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1225))

Abstract

Cancer recurrence is one of the most imminent problems in the current world of medicine, and it is responsible for most of the cancer-related death rates worldwide. Long-term administration of anticancer cytotoxic drugs may act as a double-edged sword, as necrosis may lead to renewed cancer progression and treatment resistance. The lack of nutrients, coupled with the induced hypoxia, triggers cell death and secretion of signals that affect the tumor niche. Many efforts have been made to better understand the contribution of hypoxia and metabolic stress to cancer progression and resistance, but mostly with respect to inflammation. Here we provide an overview of the direct anticancer effects of necrotic signals, which are not necessarily mediated by inflammation and the role of DAMPs (damage-associated molecular patterns) on the formation of a pro-cancerous environment.

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

References

  1. Cho YS, Park SY (2014) Harnessing of programmed necrosis for fighting against cancers. Biomol Ther (Seoul) 22:167–175

    Article  CAS  Google Scholar 

  2. Shimizu S, Eguchi Y, Kamiike W, Itoh Y, Hasegawa J, Yamabe K et al (1996) Induction of apoptosis as well as necrosis by hypoxia and predominant prevention of apoptosis by Bcl-2 and Bcl-XL. Cancer Res 56:2161–2166

    CAS  PubMed  Google Scholar 

  3. Ozaki T, Nakagawara A (2011) Role of p53 in cell death and human cancers. Cancers (Basel) 3:994–1013

    Article  CAS  PubMed Central  Google Scholar 

  4. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    Article  CAS  PubMed  Google Scholar 

  5. Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186

    Article  CAS  PubMed  Google Scholar 

  6. Facciabene A, Peng X, Hagemann IS, Balint K, Barchetti A, Wang LP et al (2011) Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells. Nature 475:226–230

    Article  CAS  PubMed  Google Scholar 

  7. Hernandez C, Huebener P, Schwabe RF (2016) Damage-associated molecular patterns in cancer: a double-edged sword. Oncogene 35:5931–5941

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Karsch-Bluman A, Feiglin A, Arbib E, Stern T, Shoval H, Schwob O et al (2019) Tissue necrosis and its role in cancer progression. Oncogene 38:1920–1935

    Article  CAS  PubMed  Google Scholar 

  9. Teicher BA (1994) Hypoxia and drug resistance. Cancer Metastasis Rev 13:139–168

    Article  CAS  PubMed  Google Scholar 

  10. Murakami Y, Matsumoto H, Roh M, Giani A, Kataoka K, Morizane Y et al (2014) Programmed necrosis, not apoptosis, is a key mediator of cell loss and DAMP-mediated inflammation in dsRNA-induced retinal degeneration. Cell Death Differ 21:270–277

    Article  CAS  PubMed  Google Scholar 

  11. Sachet M, Liang YY, Oehler R (2017) The immune response to secondary necrotic cells. Apoptosis 22:1189–1204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bartels K, Grenz A, Eltzschig HK (2013) Hypoxia and inflammation are two sides of the same coin. Proc Natl Acad Sci U S A 110:18351–18352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Taylor CT, Doherty G, Fallon PG, Cummins EP (2016) Hypoxia-dependent regulation of inflammatory pathways in immune cells. J Clin Invest 126:3716–3724

    Article  PubMed  PubMed Central  Google Scholar 

  14. Egners A, Erdem M, Cramer T (2016) The response of macrophages and neutrophils to hypoxia in the context of cancer and other inflammatory diseases. Mediat Inflamm 2016:2053646

    Article  CAS  Google Scholar 

  15. Lin N, Shay JES, Xie H, Lee DSM, Skuli N, Tang Q et al (2018) Myeloid cell hypoxia-inducible factors promote resolution of inflammation in experimental colitis. Front Immunol 9:2565

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Mehrabi M, Amini F, Mehrabi S (2018) Active role of the necrotic zone in desensitization of hypoxic macrophages and regulation of CSC-fate: a hypothesis. Front Oncol 8:235

    Article  PubMed  PubMed Central  Google Scholar 

  17. Wirtz D, Konstantopoulos K, Searson PC (2011) The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat Rev Cancer 11:512–522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chaffer CL, Weinberg RA (2011) A perspective on cancer cell metastasis. Science 331:1559–1564

    Article  CAS  PubMed  Google Scholar 

  19. Zeeshan R, Mutahir Z (2017) Cancer metastasis—tricks of the trade. Bosn J Basic Med Sci 17:172–182

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Bagri A, Kouros-Mehr H, Leong KG, Plowman GD (2010) Use of anti-VEGF adjuvant therapy in cancer: challenges and rationale. Trends Mol Med 16:122–132

    Article  CAS  PubMed  Google Scholar 

  21. Coleman RE, Seaman JJ (2001) The role of zoledronic acid in cancer: clinical studies in the treatment and prevention of bone metastases. Semin Oncol 28:11–16

    Article  CAS  PubMed  Google Scholar 

  22. Frankowski KJ, Wang C, Patnaik S, Schoenen FJ, Southall N, Li D et al (2018) Metarrestin, a perinucleolar compartment inhibitor, effectively suppresses metastasis. Sci Transl Med 10:eaap8307

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Esmatabadi MJ, Bakhshinejad B, Motlagh FM, Babashah S, Sadeghizadeh M (2016) Therapeutic resistance and cancer recurrence mechanisms: unfolding the story of tumour coming back. J Biosci 41:497–506

    Article  CAS  PubMed  Google Scholar 

  24. Simard S, Thewes B, Humphris G, Dixon M, Hayden C, Mireskandari S et al (2013) Fear of cancer recurrence in adult cancer survivors: a systematic review of quantitative studies. J Cancer Surviv 7:300–322

    Article  PubMed  Google Scholar 

  25. McIntosh A, Freedman G, Eisenberg D, Anderson P (2007) Recurrence rates and analysis of close or positive margins in patients treated without re-excision before radiation for breast cancer. Am J Clin Oncol 30:146–151

    Article  PubMed  Google Scholar 

  26. Rosell R, Lord RV, Taron M, Reguart N (2002) DNA repair and cisplatin resistance in non-small-cell lung cancer. Lung Cancer 38:217–227

    Article  PubMed  Google Scholar 

  27. Aguirre-Ghiso JA (2007) Models, mechanisms and clinical evidence for cancer dormancy. Nat Rev Cancer 7:834–846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Karsch-Bluman A, Amoyav B, Friedman N, Shoval H, Schwob O, Ella E et al (2017) High mobility group box 1 antagonist limits metastatic seeding in the lungs via reduction of cell-cell adhesion. Oncotarget 8:32706–32721

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  30. Wang M, Zhao J, Zhang L, Wei F, Lian Y, Wu Y et al (2017) Role of tumor microenvironment in tumorigenesis. J Cancer 8:761–773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Chen F, Zhuang X, Lin L, Yu P, Wang Y, Shi Y et al (2015) New horizons in tumor microenvironment biology: challenges and opportunities. BMC Med 13:45

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Yuan Y, Jiang YC, Sun CK, Chen QM (2016) Role of the tumor microenvironment in tumor progression and the clinical applications (review). Oncol Rep 35:2499–2515

    Article  CAS  PubMed  Google Scholar 

  33. Whiteside TL (2008) The tumor microenvironment and its role in promoting tumor growth. Oncogene 27:5904–5912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Rieger H, Welter M (2015) Integrative models of vascular remodeling during tumor growth. Wiley Interdiscip Rev Syst Biol Med 7:113–129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Carmeliet P, Jain RK (2000) Angiogenesis in cancer and other diseases. Nature 407:249–257

    Article  CAS  PubMed  Google Scholar 

  36. Jain RK (2014) Antiangiogenesis strategies revisited: from starving tumors to alleviating hypoxia. Cancer Cell 26:605–622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Tonnesen MG, Feng X, Clark RA (2000) Angiogenesis in wound healing. J Investig Dermatol Symp Proc 5:40–46

    Article  CAS  PubMed  Google Scholar 

  38. Breier G (2000) Angiogenesis in embryonic development—a review. Placenta 21(Suppl A):S11–S15

    Article  PubMed  Google Scholar 

  39. Ng EW, Adamis AP (2005) Targeting angiogenesis, the underlying disorder in neovascular age-related macular degeneration. Can J Ophthalmol 40:352–368

    Article  PubMed  Google Scholar 

  40. Timar J, Dome B, Fazekas K, Janovics A, Paku S (2001) Angiogenesis-dependent diseases and angiogenesis therapy. Pathol Oncol Res 7:85–94

    Article  CAS  PubMed  Google Scholar 

  41. Szekanecz Z, Koch AE (2007) Mechanisms of disease: angiogenesis in inflammatory diseases. Nat Clin Pract Rheumatol 3:635–643

    Article  CAS  PubMed  Google Scholar 

  42. Fang J, Nakamura H, Maeda H (2011) The EPR effect: unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv Drug Deliv Rev 63:136–151

    Article  CAS  PubMed  Google Scholar 

  43. Maeda H, Nakamura H, Fang J (2013) The EPR effect for macromolecular drug delivery to solid tumors: improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv Drug Deliv Rev 65:71–79

    Article  CAS  PubMed  Google Scholar 

  44. Jain RK, Martin JD, Stylianopoulos T (2014) The role of mechanical forces in tumor growth and therapy. Annu Rev Biomed Eng 16:321–346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Cohen MM Jr (2009) Judah Folkman, MD, 1933–2008: father of angiogenesis. J Craniofac Surg 20(Suppl 1):590–591

    Article  PubMed  Google Scholar 

  46. Camphausen K (2002) Portrait of an editorial board member: Judah Folkman: the father of modern angiogenesis. Cell Cycle 1:296–297

    Article  PubMed  Google Scholar 

  47. Hori K, Saito S, Nihei Y, Suzuki M, Sato Y (1999) Antitumor effects due to irreversible stoppage of tumor tissue blood flow: evaluation of a novel combretastatin A-4 derivative, AC7700. Jpn J Cancer Res 90:1026–1038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Sorensen AG, Emblem KE, Polaskova P, Jennings D, Kim H, Ancukiewicz M et al (2012) Increased survival of glioblastoma patients who respond to antiangiogenic therapy with elevated blood perfusion. Cancer Res 72:402–407

    Article  CAS  PubMed  Google Scholar 

  49. Carmeliet P, Jain RK (2011) Molecular mechanisms and clinical applications of angiogenesis. Nature 473:298–307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Vasudev NS, Reynolds AR (2014) Anti-angiogenic therapy for cancer: current progress, unresolved questions and future directions. Angiogenesis 17:471–494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Yang WH, Xu J, Mu JB, Xie J (2017) Revision of the concept of anti-angiogenesis and its applications in tumor treatment. Chronic Dis Transl Med 3:33–40

    PubMed  PubMed Central  Google Scholar 

  52. Emmett MS, Dewing D, Pritchard-Jones RO (2011) Angiogenesis and melanoma—from basic science to clinical trials. Am J Cancer Res 1:852–868

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Veytsman I, Aragon-Ching JB, Swain SM (2013) Bevacizumab and angiogenesis inhibitors in the treatment of CNS metastases: the road less travelled. Curr Mol Pharmacol 5:382

    Article  Google Scholar 

  54. Glade-Bender J, Kandel JJ, Yamashiro DJ (2003) VEGF blocking therapy in the treatment of cancer. Expert Opin Biol Ther 3:263–276

    Article  CAS  PubMed  Google Scholar 

  55. Garcia A, Singh H (2013) Bevacizumab and ovarian cancer. Ther Adv Med Oncol 5:133–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Levin VA, Bidaut L, Hou P, Kumar AJ, Wefel JS, Bekele BN et al (2011) Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Biol Phys 79:1487–1495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Cancer Genome Atlas Research Network (2011) Integrated genomic analyses of ovarian carcinoma. Nature 474:609–615

    Article  CAS  Google Scholar 

  58. Sun Y (2016) Tumor microenvironment and cancer therapy resistance. Cancer Lett 380:205–215

    Article  CAS  PubMed  Google Scholar 

  59. Bottsford-Miller JN, Coleman RL, Sood AK (2012) Resistance and escape from antiangiogenesis therapy: clinical implications and future strategies. J Clin Oncol 30:4026–4034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Son B, Lee S, Youn H, Kim E, Kim W, Youn B (2017) The role of tumor microenvironment in therapeutic resistance. Oncotarget 8:3933–3945

    Article  PubMed  Google Scholar 

  61. Zarrin B, Zarifi F, Vaseghi G, Javanmard SH (2017) Acquired tumor resistance to antiangiogenic therapy: mechanisms at a glance. J Res Med Sci 22:117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Bergers G, Hanahan D (2008) Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer 8:592–603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Casanovas O (2011) The adaptive stroma joining the antiangiogenic resistance front. J Clin Invest 121:1244–1247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Jain RK, Duda DG, Willett CG, Sahani DV, Zhu AX, Loeffler JS et al (2009) Biomarkers of response and resistance to antiangiogenic therapy. Nat Rev Clin Oncol 6:327–338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Pinto MP, Sotomayor P, Carrasco-Avino G, Corvalan AH, Owen GI (2016) Escaping antiangiogenic therapy: strategies employed by cancer cells. Int J Mol Sci 17:1489

    Article  PubMed Central  CAS  Google Scholar 

  66. Shaked Y (2016) Balancing efficacy of and host immune responses to cancer therapy: the yin and yang effects. Nat Rev Clin Oncol 13:611–626

    Article  CAS  PubMed  Google Scholar 

  67. Prager GW, Poettler M, Unseld M, Zielinski CC (2012) Angiogenesis in cancer: anti-VEGF escape mechanisms. Transl Lung Cancer Res 1:14–25

    PubMed  PubMed Central  Google Scholar 

  68. Barnett FH, Rosenfeld M, Wood M, Kiosses WB, Usui Y, Marchetti V et al (2016) Macrophages form functional vascular mimicry channels in vivo. Sci Rep 6:36659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Shiga K, Hara M, Nagasaki T, Sato T, Takahashi H, Takeyama H (2015) Cancer-associated fibroblasts: their characteristics and their roles in tumor growth. Cancers (Basel) 7:2443–2458

    Article  Google Scholar 

  70. Franco M, Roswall P, Cortez E, Hanahan D, Pietras K (2011) Pericytes promote endothelial cell survival through induction of autocrine VEGF-A signaling and Bcl-w expression. Blood 118:2906–2917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Ribeiro AL, Okamoto OK (2015) Combined effects of pericytes in the tumor microenvironment. Stem Cells Int 2015:868475

    Article  PubMed  PubMed Central  Google Scholar 

  72. Giuliano S, Pages G (2013) Mechanisms of resistance to anti-angiogenesis therapies. Biochimie 95:1110–1119

    Article  CAS  PubMed  Google Scholar 

  73. Hida K, Hida Y, Shindoh M (2008) Understanding tumor endothelial cell abnormalities to develop ideal anti-angiogenic therapies. Cancer Sci 99:459–466

    Article  CAS  PubMed  Google Scholar 

  74. Hida K, Akiyama K, Ohga N, Maishi N, Hida Y (2013) Tumour endothelial cells acquire drug resistance in a tumour microenvironment. J Biochem 153:243–249

    Article  CAS  PubMed  Google Scholar 

  75. Luqmani YA (2005) Mechanisms of drug resistance in cancer chemotherapy. Med Princ Pract 14(Suppl 1):35–48

    Article  PubMed  Google Scholar 

  76. Di Nicolantonio F, Mercer SJ, Knight LA, Gabriel FG, Whitehouse PA, Sharma S et al (2005) Cancer cell adaptation to chemotherapy. BMC Cancer 5:78

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Eltzschig HK, Carmeliet P (2011) Hypoxia and inflammation. N Engl J Med 364:656–665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Eales KL, Hollinshead KE, Tennant DA (2016) Hypoxia and metabolic adaptation of cancer cells. Oncogene 5:e190

    Article  CAS  Google Scholar 

  79. Brown JM, Wilson WR (2004) Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer 4:437–447

    Article  CAS  PubMed  Google Scholar 

  80. Muz B, de la Puente P, Azab F, Azab AK (2015) The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia (Auckl) 3:83–92

    Article  Google Scholar 

  81. Vaupel P, Mayer A (2007) Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev 26:225–239

    Article  CAS  PubMed  Google Scholar 

  82. Vaupel P (2004) The role of hypoxia-induced factors in tumor progression. Oncologist 9(Suppl 5):10–17

    Article  CAS  PubMed  Google Scholar 

  83. Wilson WR, Hay MP (2011) Targeting hypoxia in cancer therapy. Nat Rev Cancer 11:393–410

    Article  CAS  PubMed  Google Scholar 

  84. Roh JS, Sohn DH (2018) Damage-associated molecular patterns in inflammatory diseases. Immune Netw 18:e27

    Article  PubMed  PubMed Central  Google Scholar 

  85. Steinbach JP, Wolburg H, Klumpp A, Probst H, Weller M (2003) Hypoxia-induced cell death in human malignant glioma cells: energy deprivation promotes decoupling of mitochondrial cytochrome c release from caspase processing and necrotic cell death. Cell Death Differ 10:823–832

    Article  CAS  PubMed  Google Scholar 

  86. Saikumar P, Dong Z, Patel Y, Hall K, Hopfer U, Weinberg JM et al (1998) Role of hypoxia-induced Bax translocation and cytochrome c release in reoxygenation injury. Oncogene 17:3401–3415

    Article  CAS  PubMed  Google Scholar 

  87. Greijer AE, van der Wall E (2004) The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis. J Clin Pathol 57:1009–1014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Tower J (2015) Programmed cell death in aging. Ageing Res Rev 23:90–100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Lockshin RA, Zakeri Z (2007) Cell death in health and disease. J Cell Mol Med 11:1214–1224

    Article  PubMed  PubMed Central  Google Scholar 

  91. Hotchkiss RS, Strasser A, McDunn JE, Swanson PE (2009) Cell death. N Engl J Med 361:1570–1583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Muller PA, Vousden KH (2014) Mutant p53 in cancer: new functions and therapeutic opportunities. Cancer Cell 25:304–317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Amaravadi RK, Thompson CB (2007) The roles of therapy-induced autophagy and necrosis in cancer treatment. Clin Cancer Res 13:7271–7279

    Article  CAS  PubMed  Google Scholar 

  94. Diakos CI, Charles KA, McMillan DC, Clarke SJ (2014) Cancer-related inflammation and treatment effectiveness. Lancet Oncol 15:e493–e503

    Article  PubMed  Google Scholar 

  95. Chow MT, Moller A, Smyth MJ (2012) Inflammation and immune surveillance in cancer. Semin Cancer Biol 22:23–32

    Article  CAS  PubMed  Google Scholar 

  96. Herszenyi L, Lakatos G, Hritz I, Varga MZ, Cierny G, Tulassay Z (2012) The role of inflammation and proteinases in tumor progression. Dig Dis 30:249–254

    Article  PubMed  Google Scholar 

  97. Zeh HJ 3rd, Lotze MT (2005) Addicted to death: invasive cancer and the immune response to unscheduled cell death. J Immunother 28:1–9

    Article  PubMed  Google Scholar 

  98. Zitvogel L, Kroemer G (2008) The immune response against dying tumor cells: avoid disaster, achieve cure. Cell Death Differ 15:1–2

    Article  CAS  PubMed  Google Scholar 

  99. Newton K, Dixit VM (2012) Signaling in innate immunity and inflammation. Cold Spring Harb Perspect Biol 4:a006049

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Land WG (2015) The role of damage-associated molecular patterns (DAMPs) in human diseases: part II: DAMPs as diagnostics, prognostics and therapeutics in clinical medicine. Sultan Qaboos Univ Med J 15:e157–e170

    PubMed  PubMed Central  Google Scholar 

  101. Kaczmarek A, Vandenabeele P, Krysko DV (2013) Necroptosis: the release of damage-associated molecular patterns and its physiological relevance. Immunity 38:209–223

    Article  CAS  PubMed  Google Scholar 

  102. Pandolfi F, Altamura S, Frosali S, Conti P (2016) Key role of DAMP in inflammation, cancer, and tissue repair. Clin Ther 38:1017–1028

    Article  CAS  PubMed  Google Scholar 

  103. Castellani P, Balza E, Rubartelli A (2014) Inflammation, DAMPs, tumor development, and progression: a vicious circle orchestrated by redox signaling. Antioxid Redox Signal 20:1086–1097

    Article  CAS  PubMed  Google Scholar 

  104. Hagemann T, Balkwill F, Lawrence T (2007) Inflammation and cancer: a double-edged sword. Cancer Cell 12:300–301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Salah S, Lewin J, Amir E, Abdul Razak A (2018) Tumor necrosis and clinical outcomes following neoadjuvant therapy in soft tissue sarcoma: a systematic review and meta-analysis. Cancer Treat Rev 69:1–10

    Article  PubMed  Google Scholar 

  106. Hanahan D, Bergers G, Bergsland E (2000) Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice. J Clin Invest 105:1045–1047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Simsek C, Esin E, Yalcin S (2019) Metronomic chemotherapy: a systematic review of the literature and clinical experience. J Oncol 2019:5483791

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  108. Gotwals P, Cameron S, Cipolletta D, Cremasco V, Crystal A, Hewes B et al (2017) Prospects for combining targeted and conventional cancer therapy with immunotherapy. Nat Rev Cancer 17:286–301

    Article  CAS  PubMed  Google Scholar 

  109. Zahorowska B, Crowe PJ, Yang JL (2009) Combined therapies for cancer: a review of EGFR-targeted monotherapy and combination treatment with other drugs. J Cancer Res Clin Oncol 135:1137–1148

    Article  CAS  PubMed  Google Scholar 

  110. Tomes L, Emberley E, Niu Y, Troup S, Pastorek J, Strange K et al (2003) Necrosis and hypoxia in invasive breast carcinoma. Breast Cancer Res Treat 81:61–69

    Article  PubMed  Google Scholar 

  111. Eustace A, Irlam JJ, Taylor J, Denley H, Agrawal S, Choudhury A et al (2013) Necrosis predicts benefit from hypoxia-modifying therapy in patients with high risk bladder cancer enrolled in a phase III randomised trial. Radiother Oncol 108:40–47

    Article  PubMed  PubMed Central  Google Scholar 

  112. Rundqvist H, Johnson RS (2013) Tumour oxygenation: implications for breast cancer prognosis. J Intern Med 274:105–112

    Article  CAS  PubMed  Google Scholar 

  113. Liu R, Li Z, Bai S, Zhang H, Tang M, Lei Y et al (2009) Mechanism of cancer cell adaptation to metabolic stress: proteomics identification of a novel thyroid hormone-mediated gastric carcinogenic signaling pathway. Mol Cell Proteomics 8:70–85

    Article  CAS  PubMed  Google Scholar 

  114. Wellen KE, Thompson CB (2010) Cellular metabolic stress: considering how cells respond to nutrient excess. Mol Cell 40:323–332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Caino MC, Chae YC, Vaira V, Ferrero S, Nosotti M, Martin NM et al (2013) Metabolic stress regulates cytoskeletal dynamics and metastasis of cancer cells. J Clin Invest 123:2907–2920

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Rahman M, Hasan MR (2015) Cancer metabolism and drug resistance. Meta 5:571–600

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Institute for Drug Research, The School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel

    Adi Karsch-Bluman & Ofra Benny

Authors
  1. Adi Karsch-Bluman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ofra Benny
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ofra Benny .

Editor information

Editors and Affiliations

  1. Department of Radiology, Columbia University Medical Center, New York, NY, USA

    Alexander Birbrair

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Karsch-Bluman, A., Benny, O. (2020). Necrosis in the Tumor Microenvironment and Its Role in Cancer Recurrence. In: Birbrair, A. (eds) Tumor Microenvironment. Advances in Experimental Medicine and Biology, vol 1225. Springer, Cham. https://doi.org/10.1007/978-3-030-35727-6_6

Download citation

Publish with us

Policies and ethics

Search

Navigation