1932

Abstract

Disease recurrence following cancer therapy remains an intractable clinical problem and represents a major impediment to reducing the mortality attributable to malignant tumors. While research has traditionally focused on the cell-intrinsic mechanisms and mutations that render tumors refractory to both classical chemotherapeutics and targeted therapies, recent studies have begun to uncover myriad roles for the tumor microenvironment (TME) in modulating therapeutic efficacy. This work suggests that drug resistance is as much ecological as it is evolutionary. Specifically, cancers resident in organs throughout the body do not develop in isolation. Instead, tumor cells arise in the context of nonmalignant cellular components of a tissue. While the roles of these cell-extrinsic factors in cancer initiation and progression are well established, our understanding of the TME's influence on therapeutic outcome is in its infancy. Here, we focus on mechanisms by which neoplastic cells co-opt preexisting or treatment-induced signaling networks to survive chemotherapy.

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2019-03-04
2024-04-20
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Literature Cited

  1. Acharyya S, Oskarsson T, Vanharanta S, Malladi S, Kim J et al. 2012. A CXCL1 paracrine network links cancer chemoresistance and metastasis. Cell 150:1165–78
    [Google Scholar]
  2. Alexander JL, Wilson ID, Teare J, Marchesi JR, Nicholson JK, Kinross JM 2017. Gut microbiota modulation of chemotherapy efficacy and toxicity. Nat. Rev. Gastroenterol. Hepatol. 14:6356–65
    [Google Scholar]
  3. Allavena P, Mantovani A 2012. Immunology in the clinic review series, focus on cancer: tumour-associated macrophages: undisputed stars of the inflammatory tumour microenvironment. Clin. Exp. Immunol. 167:2195–205
    [Google Scholar]
  4. Appelmann I, Rillahan CD, de Stanchina E, Carbonetti G, Chen C et al. 2015. Janus kinase inhibition by ruxolitinib extends dasatinib- and dexamethasone-induced remissions in a mouse model of Ph+ ALL. Blood 125:91444–51
    [Google Scholar]
  5. Ariës IM, Jerchel IS, van den Dungen RESR, van den Berk LCJ, Boer JM et al. 2014. EMP1, a novel poor prognostic factor in pediatric leukemia regulates prednisolone resistance, cell proliferation, migration and adhesion. Leukemia 28:91828–37
    [Google Scholar]
  6. Ayala F, Dewar R, Kieran M, Kalluri R 2009. Contribution of bone microenvironment to leukemogenesis and leukemia progression. Leukemia 23:122233–41
    [Google Scholar]
  7. Bent EH, Gilbert LA, Hemann MT 2016. A senescence secretory switch mediated by PI3K/AKT/mTOR activation controls chemoprotective endothelial secretory responses. Genes Dev 30:161811–21
    [Google Scholar]
  8. Bernt KM, Hunger SP 2014. Current concepts in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia. Front. Oncol. 4:54
    [Google Scholar]
  9. Blatter S, Rottenberg S 2015. Minimal residual disease in cancer therapy–small things make all the difference. Drug Resist. Updates 21–22:1–10
    [Google Scholar]
  10. Blijham GH. 1993. Prevention and treatment of organ toxicity during high-dose chemotherapy: an overview. Anticancer Drugs 4:5527–33
    [Google Scholar]
  11. Borst P, Jonkers J, Rottenberg S 2007. What makes tumors multidrug resistant. Cell Cycle 6:222782–87
    [Google Scholar]
  12. Boyerinas B, Zafrir M, Yesilkanal AE, Price TT, Hyjek EM, Sipkins DA 2013. Adhesion to osteopontin in the bone marrow niche regulates lymphoblastic leukemia cell dormancy. Blood 121:244821–31
    [Google Scholar]
  13. Brown VI, Hulitt J, Fish J, Sheen C, Bruno M et al. 2007. Thymic stromal-derived lymphopoietin induces proliferation of pre-B leukemia and antagonizes mTOR inhibitors, suggesting a role for interleukin-7Rα signaling. Cancer Res 67:209963–70
    [Google Scholar]
  14. Calo E, Quintero-Estades JA, Danielian PS, Nedelcu S, Berman SD, Lees JA 2010. Rb regulates fate choice and lineage commitment in vivo.. Nature 466:73101110–14
    [Google Scholar]
  15. Castellarin M, Warren RL, Freeman JD, Dreolini L, Krzywinski M et al. 2012. Fusobacteriumnucleatum infection is prevalent in human colorectal carcinoma. Genome Res 22:2299–306
    [Google Scholar]
  16. Castro FV, McGinn OJ, Krishnan S, Marinov G, Li J et al. 2012. 5T4 oncofetal antigen is expressed in high risk of relapse childhood pre-B acute lymphoblastic leukemia and is associated with a more invasive and chemotactic phenotype. Leukemia 26:71487–98
    [Google Scholar]
  17. Chevallier P, Robillard N, Wuilleme-Toumi S, Méchinaud F, Harousseau J-L, Avet-Loiseau H 2004. Overexpression of Her2/neu is observed in one third of adult acute lymphoblastic leukemia patients and is associated with chemoresistance in these patients. Haematologica 89:111399–401
    [Google Scholar]
  18. Choi YL, Soda M, Yamashita Y, Ueno T, Takashima J et al. 2010. EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N. Engl. J. Med. 363:181734–39
    [Google Scholar]
  19. Coppé J-P, Patil CK, Rodier F, Sun Y, Muñoz DP et al. 2008. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLOS Biol 6:12e301
    [Google Scholar]
  20. Cordes N. 2006. Integrin-mediated cell-matrix interactions for prosurvival and antiapoptotic signaling after genotoxic injury. Cancer Lett 242:111–19
    [Google Scholar]
  21. Cordes N, Blaese MA, Meineke V, Van Beuningen D 2002. Ionizing radiation induces up-regulation of functional β 1-integrin in human lung tumour cell lines in vitro. Int. J. Radiat. Biol. 78:5347–57
    [Google Scholar]
  22. Corre I, Paris F, Huot J 2017. The p38 pathway, a major pleiotropic cascade that transduces stress and metastatic signals in endothelial cells. Oncotarget 8:3355684–714
    [Google Scholar]
  23. Cruz NM, Mencia-Trinchant N, Hassane DC, Guzman ML 2017. Minimal residual disease in acute myelogenous leukemia. Int. J. Lab. Hematol. 39:53–60
    [Google Scholar]
  24. Dalton WS. 1999. The tumor microenvironment as a determinant of drug response and resistance. Drug Resist. Updates 2:5285–88
    [Google Scholar]
  25. Damiano JS, Cress AE, Hazlehurst LA, Shtil AA, Dalton WS 1999. Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. Blood 93:51658–67
    [Google Scholar]
  26. Dauer P, Nomura A, Saluja A, Banerjee S 2017. Microenvironment in determining chemo-resistance in pancreatic cancer: neighborhood matters. Pancreatology 17:17–12
    [Google Scholar]
  27. Davalos AR, Coppe J-P, Campisi J, Desprez P-Y 2010. Senescent cells as a source of inflammatory factors for tumor progression. Cancer Metastasis Rev 29:2273–83
    [Google Scholar]
  28. de Bock CE, Ardjmand A, Molloy TJ, Bone SM, Johnstone D et al. 2012. The Fat1 cadherin is overexpressed and an independent prognostic factor for survival in paired diagnosis-relapse samples of precursor B-cell acute lymphoblastic leukemia. Leukemia 26:5918–26
    [Google Scholar]
  29. de Lourdes Perim A, Amarante MK, Guembarovski RL, de Oliveira CEC, Watanabe MAE 2015. CXCL12/CXCR4 axis in the pathogenesis of acute lymphoblastic leukemia (ALL): a possible therapeutic target. Cell. Mol. Life Sci. 72:91715–23
    [Google Scholar]
  30. de Rooij MFM, Kuil A, Geest CR, Eldering E, Chang BY et al. 2012. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood 119:112590–94
    [Google Scholar]
  31. DeFilipp Z, Khoury HJ 2015. Management of advanced-phase chronic myeloid leukemia. Curr. Hematol. Malig. Rep. 10:2173–81
    [Google Scholar]
  32. Dickreuter E, Cordes N 2017. The cancer cell adhesion resistome: mechanisms, targeting and translational approaches. Biol. Chem. 398:7721–35
    [Google Scholar]
  33. Dickreuter E, Eke I, Krause M, Borgmann K, van Vugt MA, Cordes N 2016. Targeting of β1 integrins impairs DNA repair for radiosensitization of head and neck cancer cells. Oncogene 35:111353–62
    [Google Scholar]
  34. Ding L, Ley TJ, Larson DE, Miller CA, Koboldt DC et al. 2012.a Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature 481:7382506–10
    [Google Scholar]
  35. Ding L, Saunders TL, Enikolopov G, Morrison SJ 2012.b Endothelial and perivascular cells maintain haematopoietic stem cells. Nature 481:7382457–62
    [Google Scholar]
  36. Dréan A, Goldwirt L, Verreault M, Canney M, Schmitt C et al. 2016. Blood-brain barrier, cytotoxic chemotherapies and glioblastoma. Expert Rev. Neurother. 16:111285–300
    [Google Scholar]
  37. Duan C-W, Shi J, Chen J, Wang B, Yu Y-H et al. 2014. Leukemia propagating cells rebuild an evolving niche in response to therapy. Cancer Cell 25:6778–93
    [Google Scholar]
  38. Dumont N, Liu B, Defilippis RA, Chang H, Rabban JT et al. 2013. Breast fibroblasts modulate early dissemination, tumorigenesis, and metastasis through alteration of extracellular matrix characteristics. Neoplasia 15:3249–62
    [Google Scholar]
  39. Eke I, Deuse Y, Hehlgans S, Gurtner K, Krause M et al. 2012. β1 Integrin/FAK/cortactin signaling is essential for human head and neck cancer resistance to radiotherapy. J. Clin. Investig. 122:41529–40
    [Google Scholar]
  40. Elliott T, Sethi T 2002. Integrins and extracellular matrix: a novel mechanism of multidrug resistance. Expert Rev. Anticancer Ther. 2:4449–59
    [Google Scholar]
  41. Erez N, Glanz S, Raz Y, Avivi C, Barshack I 2013. Cancer associated fibroblasts express pro-inflammatory factors in human breast and ovarian tumors. Biochem. Biophys. Res. Commun. 437:3397–402
    [Google Scholar]
  42. Fei F, Joo EJ, Tarighat SS, Schiffer I, Paz H et al. 2015. B-cell precursor acute lymphoblastic leukemia and stromal cells communicate through Galectin-3. Oncotarget 6:1311378–94
    [Google Scholar]
  43. Fei F, Stoddart S, Müschen M, Kim Y, Groffen J, Heisterkamp N 2010. Development of resistance to dasatinib in Bcr/Abl-positive acute lymphoblastic leukemia. Leukemia 24:4813–20
    [Google Scholar]
  44. Feliciano YMS, Bartlebaugh JME, Liu Y, Rivera FJS, Bhutkar A et al. 2017. PHF6 regulates phenotypic plasticity through chromatin organization within lineage-specific genes. Genes Dev 31:10973–89
    [Google Scholar]
  45. Feuerhake F, Sigg W, Höfter EA, Dimpfl T, Welsch U 2000. Immunohistochemical analysis of Bcl-2 and Bax expression in relation to cell turnover and epithelial differentiation markers in the non-lactating human mammary gland epithelium. Cell Tissue Res 299:147–58
    [Google Scholar]
  46. Friedrichs K, Ruiz P, Franke F, Gille I, Terpe HJ, Imhof BA 1995. High expression level of alpha 6 integrin in human breast carcinoma is correlated with reduced survival. Cancer Res 55:4901–6
    [Google Scholar]
  47. Friesen C, Roscher M, Hormann I, Fichtner I, Alt A et al. 2013. Cell death sensitization of leukemia cells by opioid receptor activation. Oncotarget 4:5677–90
    [Google Scholar]
  48. Fuks Z, Vlodavsky I, Andreeff M, McLoughlin M, Haimovitz-Friedman A 1992. Effects of extracellular matrix on the response of endothelial cells to radiation in vitro. Eur. J. Cancer 28A:4–5725–31
    [Google Scholar]
  49. Garrett WS. 2015. Cancer and the microbiota. Science 348:623080–86
    [Google Scholar]
  50. Gilbert LA, Hemann MT 2010. DNA damage-mediated induction of a chemoresistant niche. Cell 143:3355–66
    [Google Scholar]
  51. Gilbert LA, Hemann MT 2011. Chemotherapeutic resistance: surviving stressful situations. Cancer Res 71:155062–66
    [Google Scholar]
  52. Gilbert LA, Hemann MT 2012. Context-specific roles for paracrine IL-6 in lymphomagenesis. Genes Dev 26:151758–68
    [Google Scholar]
  53. Gomez-Sarosi L, Sun Y, Coleman I, Bianchi-Frias D, Nelson PS 2017. DNA damage induces a secretory program in the quiescent TME that fosters adverse cancer phenotypes. Mol. Cancer Res. 15:7842–51
    [Google Scholar]
  54. Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R et al. 2001. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293:5531876–80
    [Google Scholar]
  55. Grad JM, Zeng XR, Boise LH 2000. Regulation of Bcl-xL: a little bit of this and a little bit of STAT. Curr. Opin. Oncol. 12:6543–49
    [Google Scholar]
  56. Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C et al. 2009. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 138:4645–59
    [Google Scholar]
  57. Guryanova OA, Shank K, Spitzer B, Luciani L, Koche RP et al. 2016. DNMT3A mutations promote anthracycline resistance in acute myeloid leukemia via impaired nucleosome remodeling. Nat. Med. 22:121488–95
    [Google Scholar]
  58. Hsieh Y-T, Gang EJ, Geng H, Park E, Huantes S et al. 2013. Integrin alpha4 blockade sensitizes drug resistant pre-B acute lymphoblastic leukemia to chemotherapy. Blood 121:101814–18
    [Google Scholar]
  59. Hsieh YT, Gang EJ, Shishido SN, Kim HN, Pham J et al. 2014. Effects of the small-molecule inhibitor of integrin α4, TBC3486, on pre-B-ALL cells. Leukemia 28:102101–4
    [Google Scholar]
  60. Hu Z, Slayton WB 2014. Integrin VLA-5 and FAK are good targets to improve treatment response in the Philadelphia chromosome positive acute lymphoblastic leukemia. Front. Oncol. 4:112
    [Google Scholar]
  61. Hynes RO. 2004. The emergence of integrins: a personal and historical perspective. Matrix Biol 23:6333–40
    [Google Scholar]
  62. Hynes RO, Lively JC, McCarty JH, Taverna D, Francis SE et al. 2002. The diverse roles of integrins and their ligands in angiogenesis. Cold Spring Harb. Symp. Quant. Biol. 67:143–53
    [Google Scholar]
  63. Iida N, Dzutsev A, Stewart CA, Smith L, Bouladoux N et al. 2013. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 342:6161967–70
    [Google Scholar]
  64. Inoue H, Takemura H, Kawai Y, Yoshida A, Ueda T, Miyashita T 2002. Dexamethasone-resistant human Pre-B leukemia 697 cell line evolving elevation of intracellular glutathione level: an additional resistance mechanism. Jpn. J. Cancer Res. 93:5582–90
    [Google Scholar]
  65. Irwin ME, Nelson LD, Santiago-O'Farrill JM, Knouse PD, Miller CP et al. 2013. Small molecule ErbB inhibitors decrease proliferative signaling and promote apoptosis in Philadelphia chromosome-positive acute lymphoblastic leukemia. PLOS ONE 8:8e70608
    [Google Scholar]
  66. Iwamoto S, Mihara K, Downing JR, Pui C-H, Campana D 2007. Mesenchymal cells regulate the response of acute lymphoblastic leukemia cells to asparaginase. J. Clin. Investig. 117:41049–57
    [Google Scholar]
  67. Jia C. 2011. Advances in the regulation of liver regeneration. Expert Rev. Gastroenterol. Hepatol. 5:1105–21
    [Google Scholar]
  68. Kampan NC, Xiang SD, McNally OM, Stephens AN, Quinn MA, Plebanski M 2017. Immunotherapeutic interleukin-6 or interleukin-6 receptor blockade in cancer: challenges and opportunities. Curr. Med. Chem. 24: In press
    [Google Scholar]
  69. Kerbel RS, Kobayashi H, Graham CH 1994. Intrinsic or acquired drug resistance and metastasis: Are they linked phenotypes?. J. Cell. Biochem. 56:137–47
    [Google Scholar]
  70. Kerckhove N, Collin A, Condé S, Chaleteix C, Pezet D, Balayssac D 2017. Long-term effects, pathophysiological mechanisms, and risk factors of chemotherapy-induced peripheral neuropathies: a comprehensive literature review. Front. Pharmacol. 8:86
    [Google Scholar]
  71. Kharabi Masouleh B, Geng H, Hurtz C, Chan LN, Logan AC et al. 2014. Mechanistic rationale for targeting the unfolded protein response in pre-B acute lymphoblastic leukemia. PNAS 111:21E2219–28
    [Google Scholar]
  72. Klemm F, Joyce JA 2015. Microenvironmental regulation of therapeutic response in cancer. Trends Cell Biol 25:4198–213
    [Google Scholar]
  73. Konopleva M, Tabe Y, Zeng Z, Andreeff M 2009. Therapeutic targeting of microenvironmental interactions in leukemia: mechanisms and approaches. Drug Resist. Updates 12:4–5103–13
    [Google Scholar]
  74. Kostic AD, Chun E, Robertson L, Glickman JN, Gallini CA et al. 2013. Fusobacteriumnucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 14:2207–15
    [Google Scholar]
  75. Krause DS, Lazarides K, Lewis JB, von Andrian UH, Van Etten RA 2014. Selectins and their ligands are required for homing and engraftment of BCR-ABL1+ leukemic stem cells in the bone marrow niche. Blood 123:91361–71
    [Google Scholar]
  76. Krizhanovsky V, Xue W, Zender L, Yon M, Hernando E, Lowe SW 2008. Implications of cellular senescence in tissue damage response, tumor suppression, and stem cell biology. Cold Spring Harb. Symp. Quant. Biol. 73:0513–22
    [Google Scholar]
  77. Kühnl A, Gökbuget N, Stroux A, Burmeister T, Neumann M et al. 2010. High BAALC expression predicts chemoresistance in adult B-precursor acute lymphoblastic leukemia. Blood 115:183737–44
    [Google Scholar]
  78. Lamouille S, Xu J, Derynck R 2014. Molecular mechanisms of epithelial-mesenchymal transition. Nat. Rev. Mol. Cell Biol. 15:3178–96
    [Google Scholar]
  79. Laranjeira ABA, de Vasconcellos JF, Sodek L, Spago MC, Fornazim MC et al. 2012. IGFBP7 participates in the reciprocal interaction between acute lymphoblastic leukemia and BM stromal cells and in leukemia resistance to asparaginase. Leukemia 26:51001–11
    [Google Scholar]
  80. LeBien TW, Hozier J, Minowada J, Kersey JH 1979. Origin of chronic myelocytic leukemia in a precursor of pre-B lymphocytes. N. Engl. J. Med. 301:3144–47
    [Google Scholar]
  81. Liang Y, McDonnell S, Clynes M 2002. Examining the relationship between cancer invasion/metastasis and drug resistance. Curr. Cancer Drug Targets 2:3257–77
    [Google Scholar]
  82. Links M, Lewis C 1999. Chemoprotectants: a review of their clinical pharmacology and therapeutic efficacy. Drugs 57:3293–308
    [Google Scholar]
  83. Liu J, Joha S, Idziorek T, Corm S, Hetuin D et al. 2008. BCR-ABL mutants spread resistance to non-mutated cells through a paracrine mechanism. Leukemia 22:4791–99
    [Google Scholar]
  84. Lonardo E, Frias-Aldeguer J, Hermann PC, Heeschen C 2012. Pancreatic stellate cells form a niche for cancer stem cells and promote their self-renewal and invasiveness. Cell Cycle 11:71282–90
    [Google Scholar]
  85. Lu Z-R, Qiao P 2018. Drug delivery in cancer therapy, quo vadis. Mol. Pharm. 15:93603–16
    [Google Scholar]
  86. Luskin MR, Murakami MA, Manalis SR, Weinstock DM 2018. Targeting minimal residual disease: A path to cure?. Nat. Rev. Cancer 18:4255–63
    [Google Scholar]
  87. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA et al. 2004. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350:212129–39
    [Google Scholar]
  88. Ma X, Edmonson M, Yergeau D, Muzny DM, Hampton OA et al. 2015. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia. Nat. Commun. 6:16604
    [Google Scholar]
  89. Mallampati S, Leng X, Ma H, Zeng J, Li J et al. 2015. Tyrosine kinase inhibitors induce mesenchymal stem cell-mediated resistance in BCR-ABL+ acute lymphoblastic leukemia. Blood 125:192968–73
    [Google Scholar]
  90. Manabe A, Coustan-Smith E, Behm FG, Raimondi SC, Campana D 1992. Bone marrow-derived stromal cells prevent apoptotic cell death in B-lineage acute lymphoblastic leukemia. Blood 79:92370–77
    [Google Scholar]
  91. Manabe A, Murti KG, Coustan-Smith E, Kumagai M, Behm FG et al. 1994. Adhesion-dependent survival of normal and leukemic human B lymphoblasts on bone marrow stromal cells. Blood 83:3758–66
    [Google Scholar]
  92. McLean SR, Gana-Weisz M, Hartzoulakis B, Frow R, Whelan J et al. 2005. Imatinib binding and cKIT inhibition is abrogated by the cKIT kinase domain I missense mutation Val654Ala. Mol. Cancer Ther. 4:122008–15
    [Google Scholar]
  93. Meacham CE, Lawton LN, Soto-Feliciano YM, Pritchard JR, Joughin BA et al. 2015. A genome-scale in vivo loss-of-function screen identifies Phf6 as a lineage-specific regulator of leukemia cell growth. Genes Dev 29:5483–88
    [Google Scholar]
  94. Meads MB, Gatenby RA, Dalton WS 2009. Environment-mediated drug resistance: a major contributor to minimal residual disease. Nat. Rev. Cancer 9:9665–74
    [Google Scholar]
  95. Mishra S, Zhang B, Cunnick JM, Heisterkamp N, Groffen J 2006. Resistance to imatinib of Bcr/Abl P190 lymphoblastic leukemia cells. Cancer Res 66:105387–93
    [Google Scholar]
  96. Miyamoto H, Murakami T, Tsuchida K, Sugino H, Miyake H, Tashiro S 2004. Tumor-stroma interaction of human pancreatic cancer: acquired resistance to anticancer drugs and proliferation regulation is dependent on extracellular matrix proteins. Pancreas 28:138–44
    [Google Scholar]
  97. Mudry RE, Fortney JE, York T, Hall BM, Gibson LF 2000. Stromal cells regulate survival of B-lineage leukemic cells during chemotherapy. Blood 96:51926–32
    [Google Scholar]
  98. Naderi EH, Skah S, Ugland H, Myklebost O, Sandnes DL et al. 2015. Bone marrow stroma-derived PGE2 protects BCP-ALL cells from DNA damage-induced p53 accumulation and cell death. Mol. Cancer 14:114
    [Google Scholar]
  99. Nakasone ES, Askautrud HA, Kees T, Park J-H, Plaks V et al. 2012. Imaging tumor-stroma interactions during chemotherapy reveals contributions of the microenvironment to resistance. Cancer Cell 21:4488–503
    [Google Scholar]
  100. Naseem S, Hussain T, Manzoor S 2018. Interleukin-6: a promising cytokine to support liver regeneration and adaptive immunity in liver pathologies. Cytokine Growth Factor Rev 39:36–45
    [Google Scholar]
  101. Neesse A, Michl P, Frese KK, Feig C, Cook N et al. 2011. Stromal biology and therapy in pancreatic cancer. Gut 60:6861–68
    [Google Scholar]
  102. Orlowski RZ, Gercheva L, Williams C, Sutherland H, Robak T et al. 2015. A phase 2, randomized, double-blind, placebo-controlled study of siltuximab (anti-IL-6 mAb) and bortezomib versus bortezomib alone in patients with relapsed or refractory multiple myeloma. Am. J. Hematol. 90:142–49
    [Google Scholar]
  103. Oser MG, Niederst MJ, Sequist LV, Engelman JA 2015. Transformation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin. Lancet. Oncol. 16:4e165–72
    [Google Scholar]
  104. Parameswaran R, Lim M, Fei F, Abdel-Azim H, Arutyunyan A et al. 2014. Effector-mediated eradication of precursor B acute lymphoblastic leukemia with a novel Fc-engineered monoclonal antibody targeting the BAFF-R. Mol. Cancer Ther. 13:61567–77
    [Google Scholar]
  105. Perez-Andreu V, Roberts KG, Harvey RC, Yang W, Cheng C et al. 2013. Inherited GATA3 variants are associated with Ph-like childhood acute lymphoblastic leukemia and risk of relapse. Nat. Genet. 45:121494–98
    [Google Scholar]
  106. Pérez-Mancera PA, Young ARJ, Narita M 2014. Inside and out: the activities of senescence in cancer. Nat. Rev. Cancer 14:8547–58
    [Google Scholar]
  107. Peters R, Leyvraz S, Perey L 1998. Apoptotic regulation in primitive hematopoietic precursors. Blood 92:62041–52
    [Google Scholar]
  108. Qian B-Z, Pollard JW 2010. Macrophage diversity enhances tumor progression and metastasis. Cell 141:139–51
    [Google Scholar]
  109. Ramirez M, Rajaram S, Steininger RJ, Osipchuk D, Roth MA et al. 2016. Diverse drug-resistance mechanisms can emerge from drug-tolerant cancer persister cells. Nat. Commun. 7:10690
    [Google Scholar]
  110. Ramos A, Hemann MT 2017. Drugs, bugs, and cancer: Fusobacteriumnucleatum promotes chemoresistance in colorectal cancer. Cell 170:3411–13
    [Google Scholar]
  111. Rashidi A, Uy GL 2015. Targeting the microenvironment in acute myeloid leukemia. Curr. Hematol. Malig. Rep. 10:2126–31
    [Google Scholar]
  112. Reginato M, Karakashev S 2015. Progress toward overcoming hypoxia-induced resistance to solid tumor therapy. Cancer Manag. Res. 7:253
    [Google Scholar]
  113. Rhein P, Mitlohner R, Basso G, Gaipa G, Dworzak MN et al. 2010. CD11b is a therapy resistance- and minimal residual disease-specific marker in precursor B-cell acute lymphoblastic leukemia. Blood 115:183763–71
    [Google Scholar]
  114. Roskoski R. 2016. Ibrutinib inhibition of Bruton protein-tyrosine kinase (BTK) in the treatment of B cell neoplasms. Pharmacol. Res. 113:Pt. A395–408
    [Google Scholar]
  115. Salomons GS, Smets LA, Verwijs-Janssen M, Hart AA, Haarman EG et al. 1999. Bcl-2 family members in childhood acute lymphoblastic leukemia: relationships with features at presentation, in vitro and in vivo drug response and long-term clinical outcome. Leukemia 13:101574–80
    [Google Scholar]
  116. San-Miguel J, Blade J, Shpilberg O, Grosicki S, Maloisel F et al. 2014. Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti-IL-6) in multiple myeloma. Blood 123:264136–42
    [Google Scholar]
  117. Sethi T, Rintoul RC, Moore SM, MacKinnon AC, Salter D et al. 1999. Extracellular matrix proteins protect small cell lung cancer cells against apoptosis: a mechanism for small cell lung cancer growth and drug resistance in vivo. Nat. Med 5:6662–68
    [Google Scholar]
  118. Shalapour S, Hof J, Kirschner-Schwabe R, Bastian L, Eckert C et al. 2011. High VLA-4 expression is associated with adverse outcome and distinct gene expression changes in childhood B-cell precursor acute lymphoblastic leukemia at first relapse. Haematologica 96:111627–35
    [Google Scholar]
  119. Sharma SV, Lee DY, Li B, Quinlan MP, Takahashi F et al. 2010. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell 141:169–80
    [Google Scholar]
  120. Shibue T, Weinberg RA 2017. EMT, CSCs, and drug resistance: the mechanistic link and clinical implications. Nat. Rev. Clin. Oncol. 14:10611–29
    [Google Scholar]
  121. Shishido S, Banig H, Kim Y-M 2014. Role of integrin alpha4 in drug resistance of leukemia. Front. Oncol 4:99
    [Google Scholar]
  122. Shree T, Olson OC, Elie BT, Kester JC, Garfall AL et al. 2011. Macrophages and cathepsin proteases blunt chemotherapeutic response in breast cancer. Genes Dev 25:232465–79
    [Google Scholar]
  123. Singh H, Shelat AA, Singh A, Boulos N, Williams RT, Guy RK 2014. A screening-based approach to circumvent tumor microenvironment-driven intrinsic resistance to BCR-ABL+ inhibitors in Ph+ acute lymphoblastic leukemia. J. Biomol. Screen. 19:1158–67
    [Google Scholar]
  124. Sison EAR, Brown P 2011. The bone marrow microenvironment and leukemia: biology and therapeutic targeting. Expert Rev. Hematol. 4:3271–83
    [Google Scholar]
  125. Sison EAR, Magoon D, Li L, Annesley CE, Rau RE et al. 2014. Plerixafor as a chemosensitizing agent in pediatric acute lymphoblastic leukemia: efficacy and potential mechanisms of resistance to CXCR4 inhibition. Oncotarget 5:198947–58
    [Google Scholar]
  126. Spinella J-F, Richer C, Cassart P, Ouimet M, Healy J, Sinnett D 2018. Mutational dynamics of early and late relapsed childhood ALL: rapid clonal expansion and long-term dormancy. Blood Adv 2:3177–88
    [Google Scholar]
  127. St Croix B, Man S, Kerbel RS 1998. Reversal of intrinsic and acquired forms of drug resistance by hyaluronidase treatment of solid tumors. Cancer Lett 131:135–44
    [Google Scholar]
  128. Sun Y, Campisi J, Higano C, Beer TM, Porter P et al. 2012. Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B. Nat. Med. 18:91359–68
    [Google Scholar]
  129. Tam WL, Lu H, Buikhuisen J, Soh BS, Lim E et al. 2013. Protein kinase C α is a central signaling node and therapeutic target for breast cancer stem cells. Cancer Cell 24:3347
    [Google Scholar]
  130. Tanaka H, Kono E, Tran CP, Miyazaki H, Yamashiro J et al. 2010. Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance. Nat. Med. 16:121414–20
    [Google Scholar]
  131. Tang Y-C, Yuwen H, Wang K, Bruno PM, Bullock K et al. 2017. Aneuploid cell survival relies upon sphingolipid homeostasis. Cancer Res 77:195272–86
    [Google Scholar]
  132. Tavora B, Reynolds LE, Batista S, Demircioglu F, Fernandez I et al. 2014. Endothelial-cell FAK targeting sensitizes tumours to DNA-damaging therapy. Nature 514:7520112–16
    [Google Scholar]
  133. Taylor KH, Pena-Hernandez KE, Davis JW, Arthur GL, Duff DJ et al. 2007. Large-scale CpG methylation analysis identifies novel candidate genes and reveals methylation hotspots in acute lymphoblastic leukemia. Cancer Res 67:62617–25
    [Google Scholar]
  134. Tripodo C, Sangaletti S, Piccaluga PP, Prakash S, Franco G et al. 2011. The bone marrow stroma in hematological neoplasms—a guilty bystander. Nat. Rev. Clin. Oncol. 8:8456–66
    [Google Scholar]
  135. Troeger A, Gudowius S, Escherich G, den Boer ML, Glouchkova L et al. 2007. High nerve growth factor receptor (p75NTR) expression is a favourable prognostic factor in paediatric B cell precursor-acute lymphoblastic leukaemia. Br. J. Haematol. 139:3450–57
    [Google Scholar]
  136. Turkson J. 2004. STAT proteins as novel targets for cancer drug discovery. Expert Opin. Ther. Targets 8:5409–22
    [Google Scholar]
  137. van den Berk LCJ, van der Veer A, Willemse ME, Theeuwes MJGA, Luijendijk MW et al. 2014. Disturbed CXCR4/CXCL12 axis in paediatric precursor B-cell acute lymphoblastic leukaemia. Br. J. Haematol. 166:2240–49
    [Google Scholar]
  138. van den Heuvel-Eibrink MM, Wiemer EA, Kuijpers M, Pieters R, Sonneveld P 2001. Absence of mutations in the deoxycytidine kinase (dCK) gene in patients with relapsed and/or refractory acute myeloid leukemia (AML). Leukemia 15:5855–56
    [Google Scholar]
  139. van Tellingen O, Yetkin-Arik B, de Gooijer MC, Wesseling P, Wurdinger T, de Vries HE 2015. Overcoming the blood-brain tumor barrier for effective glioblastoma treatment. Drug Resist. Updates 19:1–12
    [Google Scholar]
  140. Vera-Ramirez L, Hunter KW 2017. Tumor cell dormancy as an adaptive cell stress response mechanism. F1000Research 6:2134
    [Google Scholar]
  141. Wagle N, Emery C, Berger MF, Davis MJ, Sawyer A et al. 2011. Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling. J. Clin. Oncol. 29:223085–96
    [Google Scholar]
  142. Welschinger R, Liedtke F, Basnett J, Dela Pena A, Juarez JG et al. 2013. Plerixafor (AMD3100) induces prolonged mobilization of acute lymphoblastic leukemia cells and increases the proportion of cycling cells in the blood in mice. Exp. Hematol. 41:3293–302.e1
    [Google Scholar]
  143. Williams RT, den Besten W, Sherr CJ 2007. Cytokine-dependent imatinib resistance in mouse BCR-ABL+, Arf-null lymphoblastic leukemia. Genes Dev 21:182283–87
    [Google Scholar]
  144. Williams RT, Roussel MF, Sherr CJ 2006. Arf gene loss enhances oncogenicity and limits imatinib response in mouse models of Bcr-Abl-induced acute lymphoblastic leukemia. PNAS 103:176688–93
    [Google Scholar]
  145. Winkler B, Taschik J, Haubitz I, Eyrich M, Schlegel PG, Wiegering V 2015. TGFβ and IL10 have an impact on risk group and prognosis in childhood ALL. Pediatr. Blood Cancer 62:172–79
    [Google Scholar]
  146. Ye H, Adane B, Khan N, Sullivan T, Minhajuddin M et al. 2016. Leukemic stem cells evade chemotherapy by metabolic adaptation to an adipose tissue niche. Cell Stem Cell 19:123–37
    [Google Scholar]
  147. Yu M, Gang EJ, Parameswaran R, Stoddart S, Fei F et al. 2011. AMD3100 sensitizes acute lymphoblastic leukemia cells to chemotherapy in vivo. Blood Cancer J 1:4e14
    [Google Scholar]
  148. Yu T, Guo F, Yu Y, Sun T, Ma D et al. 2017. Fusobacteriumnucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell 170:3548–63.e16
    [Google Scholar]
  149. Zhang Y, Hu K, Hu Y, Liu L, Wang B, Huang H 2014. Bone marrow mesenchymal stromal cells affect the cell cycle arrest effect of genotoxic agents on acute lymphocytic leukemia cells via p21 down-regulation. Ann. Hematol. 93:91499–508
    [Google Scholar]
  150. Zhang Z, Vuori K, Reed JC, Ruoslahti E 1995. The α5β1 integrin supports survival of cells on fibronectin and up-regulates Bcl-2 expression. PNAS 92:136161–65
    [Google Scholar]
  151. Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J et al. 2001. 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. 7:91028–34
    [Google Scholar]
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