1. National Center for Health Statistics. Health, United States, 2015: with special feature on racial and ethnic health disparities. Hyattsville, MD: 2016.

2. American Cancer Society. Cancer Facts & Figures 2017. Atlanta: American Cancer Society; 2017.

3. Housman G, Byler S, Heerboth S, Lapinska K, Longacre M, et al. Drug resistance in cancer: an overview. Cancers (Basel) 2014;6:1769-92.

4. Rueff J, Rodrigues AS. Cancer drug resistance: a brief overview from a genetic viewpoint. Methods Mol Biol 2016:1395:1-18.

5. Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug resistance: an evolving paradigm. Nat Rev Cancer 2013;13:714-26.

6. Borst P. Cancer drug pan-resistance: pumps, cancer stem cells, quiescence, epithelial to mesenchymal transition, blocked cell death pathways, persisters or what? Open Biol 2012;2:120066.

7. Alfarouk KO, Stock CM, Taylor S, Walsh M, Muddathir AK, et al. Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp. Cancer Cell Int 2015;15:71.

8. Urruticoechea A, Alemany R, Balart J, Villanueva A, Viñals F, et al. Recent advances in cancer therapy: an overview. Curr Pharm Des 2010;16:3-10.

9. Baskar R, Lee KA, Yeo R, Yeoh KW. Cancer and radiation therapy: current advances and future directions. Int J Med Sci 2012;9:193-9.

10. Damin DC, Lazzaron AR. Evolving treatment strategies for colorectal cancer: a critical review of current therapeutic options. World J Gastroenterol 2014;20:877.

11. Lumachi F, Luisetto G, Basso SMM, Basso U, Brunello A, et al. Endocrine therapy of breast cancer. Curr Med Chem 2011;18:513-22.

12. Khalil DN, Smith EL, Brentjens RJ, Wolchok JD. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat Rev Clin Oncol 2016;13:273-90.

13. Uramoto H, Tanaka F. Recurrence after surgery in patients with NSCLC. Transl lung cancer Res 2014;3:242-9.

14. Castells M, Thibault B, Delord JP, Couderc B. Implication of tumor microenvironment in chemoresistance: tumor-associated stromal cells protect tumor cells from cell death. Int J Mol Sci 2012;13:9545-71.

15. O’Connor D, Sibson K, Caswell M, Connor P, Cummins M, et al. Early UK experience in the use of clofarabine in the treatment of relapsed and refractory paediatric acute lymphoblastic leukaemia. Br J Haematol 2011;154:482-5.

16. Lippert T, Ruoff HJ, Volm M. Intrinsic and acquired drug resistance in malignant tumors. Arzneimittelforschung 2008;58:261-4.

17. Kelderman S, Schumacher TN, Haanen JB. Acquired and intrinsic resistance in cancer immunotherapy. Mol Oncol 2014;8:1132-9.

18. Huang D, Duan H, Huang H, Tong X, Han Y, et al. Cisplatin resistance in gastric cancer cells is associated with HER2 upregulation-induced epithelial-mesenchymal transition. Sci Rep 2016;6:20502.

19. Kurrey NK, Jalgaonkar SP, Joglekar AV, Ghanate AD, Chaskar PD, et al. Snail and Slug mediate radioresistance and chemoresistance by antagonizing p53-mediated apoptosis and acquiring a stem-like phenotype in ovarian cancer cells. Stem Cells 2009;27:2059-68.

20. Witta SE, Gemmill RM, Hirsch FR, Coldren CD, Hedman K, et al. Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines. Cancer Res 2006;66:944-50.

21. Sayan AE, Griffiths TR, Pal R, Browne GJ, Ruddick A, et al. SIP1 protein protects cells from DNA damage-induced apoptosis and has independent prognostic value in bladder cancer. Proc Natl Acad Sci U S A 2009;106:14884-9.

22. Burrell RA, McGranahan N, Bartek J, Swanton C. The causes and consequences of genetic heterogeneity in cancer evolution. Nature 2013;501:338-45.

23. Kreso A, Dick JE. Evolution of the cancer stem cell model. Cell Stem Cell 2014;14:275-91.

24. Turner NC, Reis-Filho JS. Genetic heterogeneity and cancer drug resistance. Lancet Oncol 2012;13:e178-85.

25. Moulder S. Intrinsic resistance to chemotherapy in breast cancer. Women’s Heal 2010;6:821-30.

26. Greaves M, Maley CC. Clonal evolution in cancer. Nature 2012;481:306-13.

27. Kuczynski EA, Sargent DJ, Grothey A, Kerbel RS. Drug rechallenge and treatment beyond progression--implications for drug resistance. Nat Rev Clin Oncol 2013;10:571-87.

28. Frank NY, Schatton T, Frank MH, Geles K, Grindley J, et al. The therapeutic promise of the cancer stem cell concept. J Clin Invest 2010;120:41-50.

29. Viale A, De Franco F, Orleth A, Cambiaghi V, Giuliani V, et al. Cell-cycle restriction limits DNA damage and maintains self-renewal of leukaemia stem cells. Nature 2009;457:51-6.

30. Eramo A, Ricci-Vitiani L, Zeuner A, Pallini R, Lotti F, et al. Chemotherapy resistance of glioblastoma stem cells. Cell Death Differ 2006;13:1238-41.

31. Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, et al. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 2007;1:313-23.

32. Gillet JP, Calcagno AM, Varma S, Davidson B, Bunkholt Elstrand M, et al. Multidrug resistance-linked gene signature predicts overall survival of patients with primary ovarian serous carcinoma. Clin Cancer Res 2012;18:3197-206.

33. Traverso N, Ricciarelli R, Nitti M, Marengo B, Furfaro AL, et al. Role of glutathione in cancer progression and chemoresistance. Oxid Med Cell Longev 2013;2013:972913.

34. Ding L, Ley TJ, Larson DE, Miller CA, Koboldt DC, et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature 2012;481:506-10.

35. Quintás-Cardama A, Kantarjian HM, Cortes JE. Mechanisms of primary and secondary resistance to imatinib in chronic myeloid leukemia. Cancer Control 2009;16:122-31.

36. Jabbour EJ, Cortes JE, Kantarjian HM. Resistance to tyrosine kinase inhibition therapy for chronic myelogenous leukemia: a clinical perspective and emerging treatment options. Clin Lymphoma Myeloma Leuk 2013;13:515-29.

37. Kimura S, Ando T, Kojima K. BCR-ABL point mutations and TKI treatment in CML patients. J Hematol Transfus 2014;2.

38. Challagundla KB, Wise PM, Neviani P, Chava H, Murtadha M, et al. Exosome-mediated transfer of microRNAs within the tumor microenvironment and neuroblastoma resistance to chemotherapy. J Natl Cancer Inst 2015;107:djv135.

39. Vadlapatla R, Vadlapudi A, Pal D, Mitra A. Mechanisms of drug resistance in cancer chemotherapy: coordinated role and regulation of efflux transporters and metabolizing enzymes. Curr Pharm Des 2013;19:7126-40.

40. Wu Q, Yang Z, Nie Y, Shi Y, Fan D. Multi-drug resistance in cancer chemotherapeutics: Mechanisms and lab approaches. Cancer Lett 2014;347:159-66.

41. Vasiliou V, Vasiliou K, Nebert DW. Human ATP-binding cassette (ABC) transporter family. Hum Genomics 2009;3:281-90.

42. Wilkens S. Structure and mechanism of ABC transporters. F1000Prime Rep 2015;7:14.

43. Sauna ZE, Kim IW, Ambudkar SV. Genomics and the mechanism of P-glycoprotein (ABCB1). J Bioenerg Biomembr 2007;39:481-7.

44. Lagas JS, Fan L, Wagenaar E, Vlaming ML, van Tellingen O, et al. P-glycoprotein (P-gp/Abcb1), Abcc2, and Abcc3 determine the pharmacokinetics of etoposide. Clin Cancer Res 2010;16:130-40.

45. Lal S, Wong ZW, Sandanaraj E, Xiang X, Ang PC, et al. Influence of ABCB1 and ABCG2 polymorphisms on doxorubicin disposition in Asian breast cancer patients. Cancer Sci 2008;99:816-23.

46. Vaidyanathan A, Sawers L, Gannon AL, Chakravarty P, Scott AL, et al. ABCB1 (MDR1) induction defines a common resistance mechanism in paclitaxel- and olaparib-resistant ovarian cancer cells. Br J Cancer 2016;115:431-41.

47. Satake K, Tsukamoto M, Mitani Y, Regasini LO, da Silva Bolzani V, et al. Human ABCB1 confers cells resistance to cytotoxic guanidine alkaloids from Pterogyne nitens. Biomed Mater Eng 2015;25:249-56.

48. Sharom FJ. ABC multidrug transporters: structure, function and role in chemoresistance. Pharmacogenomics 2008;9:105-27.

49. Fojo AT, Ueda K, Slamon DJ, Poplack DG, Gottesman MM, et al. Expression of a multidrug-resistance gene in human tumors and tissues. Proc Natl Acad Sci U S A 1987;84:265-9.

50. Shaffer BC, Gillet JP, Patel C, Baer MR, Bates SE, et al. Drug resistance: still a daunting challenge to the successful treatment of AML. Drug Resist Updat 2012;15:62-9.

51. Baudis M, Prima V, Tung YH, Hunger SP. ABCB1 over-expression and drug-efflux in acute lymphoblastic leukemia cell lines with t(17;19) and E2A-HLF expression. Pediatr Blood Cancer 2006;47:757-64.

52. Peng XX, Tiwari AK, Wu HC, Chen ZS. Overexpression of P-glycoprotein induces acquired resistance to imatinib in chronic myelogenous leukemia cells. Chin J Cancer 2012;31:110-8.

53. Yin J, Zhang J. Multidrug resistance-associated protein 1 (MRP1/ABCC1) polymorphism: from discovery to clinical application. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2011;36:927-38.

54. Müller M, Meijer C, Zaman GJ, Borst P, Scheper RJ, Mulder NH, et al. Overexpression of the gene encoding the multidrug resistance-associated protein results in increased ATP-dependent glutathione S-conjugate transport. Proc Natl Acad Sci U S A 1994;91:13033-7.

55. Cole SPC, Deeley RG. Transport of glutathione and glutathione conjugates by MRP1. Trends Pharmacol Sci 2006;27:438-46.

56. Cole SP. Multidrug resistance protein 1 (MRP1, ABCC1), a “multitasking” ATP-binding cassette (ABC) transporter. J Biol Chem 2014;289:30880-8.

57. Munoz M, Henderson M, Haber M, Norris M. Role of the MRP1/ABCC1 multidrug transporter protein in cancer. IUBMB Life 2007;59:752-7.

58. Cho S, Lu M, He X, Ee PL, Bhat U, et al. Notch1 regulates the expression of the multidrug resistance gene ABCC1/MRP1 in cultured cancer cells. Proc Natl Acad Sci U S A 2011;108:20778-83.

59. Stacy AE, Jansson PJ, Richardson DR. Molecular pharmacology of ABCG2 and Its role in chemoresistance. Mol Pharmacol 2013;84:655-69.

60. Mao Q, Unadkat JD. Role of the breast cancer resistance protein (BCRP/ABCG2) in drug transport--an update. AAPS J 2015;17:65-82.

61. Horsey AJ, Cox MH, Sarwat S, Kerr ID. The multidrug transporter ABCG2: still more questions than answers Multidrug transporters in biology. Biochem Soc Trans 2016;44:824-30.

62. Pan ST, Li ZL, He ZX, Qiu JX, Zhou SF. Molecular mechanisms for tumour resistance to chemotherapy. Clin Exp Pharmacol Physiol 2016;43:723-37.

63. Folmer Y, Schneider M, Blum HE, Hafkemeyer P. Reversal of drug resistance of hepatocellular carcinoma cells by adenoviral delivery of anti-ABCC2 antisense constructs. Cancer Gene Ther 2007;14:875-84.

64. Balaji SA, Udupa N, Chamallamudi MR, Gupta V, Rangarajan A. Role of the drug transporter ABCC3 in breast cancer chemoresistance. PLoS One 2016;11:e0155013.

65. Zhao Y, Lu H, Yan A, Yang Y, Meng Q, et al. ABCC3 as a marker for multidrug resistance in non-small cell lung cancer. Sci Rep 2013;3:3120.

66. Wang Y, Schmid-Bindert G, Zhou C. Erlotinib in the treatment of advanced non-small cell lung cancer: an update for clinicians. Ther Adv Med Oncol 2012;4:19-29.

67. Gridelli C, De Marinis F, Di Maio M, Cortinovis D, Cappuzzo F, et al. Gefitinib as first-line treatment for patients with advanced non-small-cell lung cancer with activating epidermal growth factor receptor mutation: review of the evidence. Lung Cancer 2011;71:249-57.

68. Tang J, Salama R, Gadgeel SM, Sarkar FH, Ahmad A. Erlotinib resistance in lung cancer: current progress and future perspectives. Front Pharmacol 2013;4:15.

69. Bell DW, Gore I, Okimoto RA, Godin-Heymann N, Sordella R, et al. Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR. Nat Genet 2005;37:1315-6.

70. Ma C, Wei S, Song Y. T790M and acquired resistance of EGFR TKI: a literature review of clinical reports. J Thorac Dis 2011;3:10-8.

71. Chan BA, Hughes BGM. Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. Transl lung cancer Res 2015;4:36-54.

72. Liao BC, Lin CC, Yang JC. Second and third-generation epidermal growth factor receptor tyrosine kinase inhibitors in advanced nonsmall cell lung cancer. Curr Opin Oncol 2015;27:94-101.

73. Wang S, Cang S, Liu D. Third-generation inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer. J Hematol Oncol 2016;9:34.

74. Wang S, Tsui ST, Liu C, Song Y, Liu D. EGFR C797S mutation mediates resistance to third-generation inhibitors in T790M-positive non-small cell lung cancer. J Hematol Oncol 2016;9:59.

75. Jia Y, Yun CH, Park E, Ercan D, Manuia M, et al. Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors. Nature 2016;534:129-32.

76. Wang S, Song Y, Liu D. EAI045: the fourth-generation EGFR inhibitor overcoming T790M and C797S resistance. Cancer Lett 2017;385:51-4.

77. MacGregor Schafer J, Liu H, Bentrem DJ, Zapf JW, Jordan VC. Allosteric silencing of activating function 1 in the 4-hydroxytamoxifen estrogen receptor complex is induced by substituting glycine for aspartate at amino acid 351. Cancer Res 2000;60:5097-105.

78. Likhite VS, Stossi F, Kim K, Katzenellenbogen BS, Katzenellenbogen JA. Kinase-specific phosphorylation of the estrogen receptor changes receptor interactions with ligand, deoxyribonucleic acid, and coregulators associated with alterations in estrogen and tamoxifen activity. Mol Endocrinol 2006;20:3120-32.

79. Avvaru SP, Noolvi MN, Aminbhavi TM, Chkraborty S, Dash A, et al. Aromatase inhibitors evolution as potential class of drugs in the treatment of postmenopausal breast cancer women. Mini Rev Med Chem 2018;18:609-21.

80. Helleday T, Petermann E, Lundin C, Hodgson B, Sharma RA. DNA repair pathways as targets for cancer therapy. Nat Rev Cancer 2008;8:193-204.

81. de Angelis PM, Fjell B, Kravik KL, Haug T, Tunheim SH, et al. Molecular characterizations of derivatives of HCT116 colorectal cancer cells that are resistant to the chemotherapeutic agent 5-fluorouracil. Int J Oncol 2004;24:1279-88.

82. De Angelis PM, Svendsrud DH, Kravik KL, Stokke T. Cellular response to 5-fluorouracil (5-FU) in 5-FU-resistant colon cancer cell lines during treatment and recovery. Mol Cancer 2006;5:20.

83. Campisi J. Aging, cellular senescence, and cancer. Annu Rev Physiol 2013;75:685-705.

84. Gordon RR, Nelson PS. Cellular senescence and cancer chemotherapy resistance. Drug Resist Updat 2012;15:123-31.

85. Schmitt CA, Fridman JS, Yang M, Lee S, Baranov E, et al. A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell 2002;109:335-46.

86. Demaria M, O’Leary MN, Chang J, Shao L, Liu S, et al. Cellular senescence promotes adverse effects of chemotherapy and cancer relapse. Cancer Discov 2017;7:165-76.

87. Roberson RS, Kussick SJ, Vallieres E, Chen SY, Wu DY. Escape from therapy-induced accelerated cellular senescence in p53-null lung cancer cells and in human lung cancers. Cancer Res 2005;65:2795-803.

88. Sabisz M, Skladanowski A. Cancer stem cells and escape from drug-induced premature senescence in human lung tumor cells: implications for drug resistance and in vitro drug screening models. Cell Cycle Georget Tex 2009;8:3208-17.

89. Milanovic M, Fan DNY, Belenki D, Däbritz JHM, Zhao Z, et al. Senescence-associated reprogramming promotes cancer stemness. Nature 2018;553:96-100.

90. Lantermann AB, McCutcheon KJ, Sharma SV. The role of epigenetics in drug resistance in cancer. Epigenetic Diagnosis Ther 2016;1:106-19.

91. Easwaran H, Tsai HC, Baylin SB. Cancer epigenetics: tumor heterogeneity, plasticity of stem-like states, and drug resistance. Mol Cell 2014;54:716-27.

92. Wilting RH, Dannenberg JH. Epigenetic mechanisms in tumorigenesis, tumor cell heterogeneity and drug resistance. Drug Resist Updat 2012;15:21-38.

93. Hoey T. Drug resistance, epigenetics, and tumor cell heterogeneity. Sci Transl Med 2010;2:28ps19.

94. Zeller C, Brown R. Therapeutic modulation of epigenetic drivers of drug resistance in ovarian cancer. Ther Adv Med Oncol 2010;2:319-29.

95. Ohata Y, Shimada S, Akiyama Y, Mogushi K, Nakao K, et al. Acquired resistance with epigenetic alterations under long-term anti-angiogenic therapy for hepatocellular carcinoma. Mol Cancer Ther 2017;16:1155-65.

96. Chen QN, Wei CC, Wang ZX, Sun M. Long non-coding RNAs in anti-cancer drug resistance. Oncotarget 2017;8:1925-36.

97. Malek E, Jagannathan S, Driscoll JJ. Correlation of long non-coding RNA expression with metastasis, drug resistance and clinical outcome in cancer. Oncotarget 2014;5:8027-38.

98. Fan Y, Shen B, Tan M, Mu X, Qin Y, et al. Long non-coding RNA UCA1 increases chemoresistance of bladder cancer cells by regulating Wnt signaling. FEBS J 2014;281:1750-8.

99. Chen X, Qian Y, Wu S. The Warburg effect: evolving interpretations of an established concept. Free Radic Biol Med 2015;79:253-63.

100. Bashashati A, Ha G, Tone A, Ding J, Prentice LM, et al. Distinct evolutionary trajectories of primary high-grade serous ovarian cancers revealed through spatial mutational profiling. J Pathol 2013;231:21-34.

101. Gerlinger M, Rowan AJ, Horswell S, Math M, Larkin J, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 2012;366:883-92.

102. Navin N, Krasnitz A, Rodgers L, Cook K, Meth J, et al. Inferring tumor progression from genomic heterogeneity. Genome Res 2010;20:68-80.

103. Landau DA, Carter SL, Stojanov P, McKenna A, Stevenson K, et al. Evolution and impact of subclonal mutations in chronic lymphocytic leukemia. Cell 2013;152:714-26.

104. Burrell RA, Swanton C. Tumour heterogeneity and the evolution of polyclonal drug resistance. Mol Oncol 2014;8:1095-111.

105. Chen W, Liu X, Lv M, Chen L, Zhao JH, et al. Exosomes from drug-resistant breast cancer cells transmit chemoresistance by a horizontal transfer of microRNAs. PLoS One 2014;9:e95240.

106. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646-74.

107. Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 2012;21:309-22.

108. Casey JR, Grinstein S, Orlowski J. Sensors and regulators of intracellular pH. Nat Rev Mol Cell Biol 2010;11:50-61.

109. Swietach P, Vaughan-Jones RD, Harris AL, Hulikova A. The chemistry, physiology and pathology of pH in cancer. Philos Trans R Soc Lond B Biol Sci 2014;369:20130099.

110. Sharma M, Astekar M, Soi S, Manjunatha B, Shetty D, et al. pH gradient reversal: an emerging hallmark of cancers. Recent Pat Anticancer Drug Discov 2015;10:244-58.

111. Taylor S, Spugnini EP, Assaraf YG, Azzarito T, Rauch C, et al. Microenvironment acidity as a major determinant of tumor chemoresistance: proton pump inhibitors (PPIs) as a novel therapeutic approach. Drug Resist Updat 2015;23:69-78.

112. Webb BA, Chimenti M, Jacobson MP, Barber DL. Dysregulated pH: a perfect storm for cancer progression. Nat Rev Cancer 2011;11:671-7.

113. Wojtkowiak JW, Verduzco D, Schramm KJ, Gillies RJ. Drug resistance and cellular adaptation to tumor acidic pH microenvironment. Mol Pharm 2011;8:2032-8.

114. Azzarito T, Venturi G, Cesolini A, Fais S. Lansoprazole induces sensitivity to suboptimal doses of paclitaxel in human melanoma. Cancer Lett 2015;356:697-703.

115. Quail DF, Bowman RL, Akkari L, Akkari L, Quick ML, et al. The tumor microenvironment underlies acquired resistance to CSF-1R inhibition in gliomas. Science 2016;352:aad3018.

116. De Palma M, Lewis CE. Macrophage regulation of tumor responses to anticancer therapies. Cancer Cell 2013;23:277-86.

117. Tap WD, Wainberg ZA, Anthony SP, Ibrahim PN, Zhang C, et al. Structure-guided blockade of CSF1R kinase in tenosynovial giant-cell tumor. N Engl J Med 2015;373:428-37.

118. Pyonteck SM, Akkari L, Schuhmacher AJ, Bowman RL, Sevenich L, et al. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat Med 2013;19:1264-72.

119. Ries CH, Cannarile MA, Hoves S, Benz J, Wartha K, et al. Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell 2014;25:846-59.

120. Reynolds TY, Rockwell S, Glazer PM. Genetic instability induced by the tumor microenvironment. Cancer Res 1996;56:5754-7.

121. Bindra RS, Glazer PM. Genetic instability and the tumor microenvironment: towards the concept of microenvironment-induced mutagenesis. Mutat Res Mol Mech Mutagen 2005;569:75-85.

122. Fischer KR, Durrans A, Lee S, Sheng J, Li F, et al. Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature 2015;527:472-6.

123. Du B, Shim J. Targeting epithelial-mesenchymal transition (EMT) to overcome drug resistance in cancer. Molecules 2016;21:965.

124. Brunen D, Willems SM, Kellner U, Midgley R, Simon I, et al. TGF-β: an emerging player in drug resistance. Cell Cycle 2013;12:2960-8.

125. Oshimori N, Oristian D, Fuchs E. TGF-β promotes heterogeneity and drug resistance in squamous cell carcinoma. Cell 2015;160:963-76.

126. Li J, Liu H, Yu J, Yu H. Chemoresistance to doxorubicin induces epithelial-mesenchymal transition via upregulation of transforming growth factor β signaling in HCT116 colon cancer cells. Mol Med Rep 2015;12:192-8.

127. Bhola NE, Balko JM, Dugger TC, Kuba MG, Sánchez V, et al. TGF-β inhibition enhances chemotherapy action against triple-negative breast cancer. J Clin Invest 2013;123:1348-58.

128. Wu Y, Ginther C, Kim J, Mosher N, Chung S, et al. Expression of Wnt3 activates Wnt/β-catenin pathway and promotes EMT-like phenotype in trastuzumab-resistant HER2-overexpressing breast cancer cells. Mol cancer Res MCR 2012;10:1597-606.

129. Della Corte CM, Bellevicine C, Vicidomini G, Vitagliano D, Malapelle U, et al. SMO gene amplification and activation of the hedgehog pathway as novel mechanisms of resistance to anti-epidermal growth factor receptor drugs in human lung cancer. Clin Cancer Res 2015;21:4686-97.

130. Shibue T, Weinberg RA. EMT, CSCs, and drug resistance: the mechanistic link and clinical implications. Nat Rev Clin Oncol 2017;14:611-29.

131. Deng JJ, Zhang W, Xu XM, Zhang F, Tao WP, et al. Twist mediates an aggressive phenotype in human colorectal cancer cells. Int J Oncol 2016;48:1117-24.

132. Haslehurst AM, Koti M, Dharsee M, Nuin P, Evans K, et al. EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer. BMC Cancer 2012;12:91.

133. Siebzehnrubl FA, Silver DJ, Tugertimur B, Deleyrolle LP, Siebzehnrubl D, et al. The ZEB1 pathway links glioblastoma initiation, invasion and chemoresistance. EMBO Mol Med 2013;5:1196-212.

134. Lazarova D, Bordonaro M. ZEB1 mediates drug resistance and EMT in p300-deficient CRC. J Cancer 2017;8:1453-9.

135. Zhou Z, Zhang L, Xie B, Wang X, Yang X, et al. FOXC2 promotes chemoresistance in nasopharyngeal carcinomas via induction of epithelial mesenchymal transition. Cancer Lett 2015;363:137-45.

136. Zheng X, Carstens JL, Kim J, Scheible M, Kaye J, et al. Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature 2015;527:525-30.

137. Saxena M, Stephens MA, Pathak H, Rangarajan A. Transcription factors that mediate epithelial-mesenchymal transition lead to multidrug resistance by upregulating ABC transporters. Cell Death Dis 2011;2:e179.

138. Zhu K, Chen L, Han X, Wang J, Wang J. Short hairpin RNA targeting Twist1 suppresses cell proliferation and improves chemosensitivity to cisplatin in HeLa human cervical cancer cells. Oncol Rep 2012;27:1027-34.

139. Tsou SH, Chen TM, Hsiao HT, Chen YH. A critical dose of doxorubicin is required to alter the gene expression profiles in MCF-7 cells acquiring multidrug resistance. PLoS One 2015;10:e0116747.

140. Li W, Liu C, Tang Y, Li H, Zhou F, et al. Overexpression of Snail accelerates adriamycin induction of multidrug resistance in breast cancer cells. Asian Pac J Cancer Prev 2011;12:2575-80.

141. Chen WJ, Wang H, Tang Y, Liu CL, Li HL, et al. Multidrug resistance in breast cancer cells during epithelial-mesenchymal transition is modulated by breast cancer resistant protein. Chin J Cancer 2010;29:151-7.

142. Hamada S, Satoh K, Hirota M, Kanno A, Umino J, et al. The homeobox gene MSX2 determines chemosensitivity of pancreatic cancer cells via the regulation of transporter gene ABCG2. J Cell Physiol 2012;227:729-38.

143. Lee SH, Oh SY, Do SI, Lee HJ, Kang HJ, et al. SOX2 regulates self-renewal and tumorigenicity of stem-like cells of head and neck squamous cell carcinoma. Br J Cancer 2014;111:2122-30.

144. Mato E, González C, Moral A, Pérez JI, Bell O, et al. ABCG2/BCRP gene expression is related to epithelial-mesenchymal transition inducer genes in a papillary thyroid carcinoma cell line (TPC-1). J Mol Endocrinol 2014;52:289-300.

145. Sun L, Ke J, He Z, Chen Z, Huang Q, et al. HES1 promotes colorectal cancer cell resistance to 5-Fu by inducing of EMT and ABC transporter proteins. J Cancer 2017;8:2802-8.

146. Uchibori K, Kasamatsu A, Sunaga M, Yokota S, Sakurada T, et al. Establishment and characterization of two 5-fluorouracil-resistant hepatocellular carcinoma cell lines. Int J Oncol 2012;40:1005-10.

147. Bhuvanalakshmi G, Arfuso F, Millward M, Dharmarajan A, Warrier S. Secreted frizzled-related protein 4 inhibits glioma stem-like cells by reversing epithelial to mesenchymal transition, inducing apoptosis and decreasing cancer stem cell properties. PLoS One 2015;10:e0127517.

148. Hou Y, Zhu Q, Li Z, Peng Y, Yu X, et al. The FOXM1-ABCC5 axis contributes to paclitaxel resistance in nasopharyngeal carcinoma cells. Cell Death Dis 2017;8:e2659.

149. Jiang ZS, Sun YZ, Wang SM, Ruan JS. Epithelial-mesenchymal transition: potential regulator of ABC transporters in tumor progression. J Cancer 2017;8:2319-27.

150. Haenisch S, Werk AN, Cascorbi I. MicroRNAs and their relevance to ABC transporters. Br J Clin Pharmacol 2014;77:587-96.

151. Lopes-Rodrigues V, Seca H, Sousa D, Sousa E, Lima RT, et al. The network of P-glycoprotein and microRNAs interactions. Int J Cancer 2014;135:253-63.

152. Liu S, Tetzlaff MT, Cui R, Xu X. miR-200c inhibits melanoma progression and drug resistance through down-regulation of Bmi-1. Am J Pathol 2012;181:1823-35.

153. Sui H, Cai GX, Pan SF, Deng WL, Wang YW, et al. miR200c attenuates P-gp-mediated MDR and metastasis by targeting JNK2/c-Jun signaling pathway in colorectal cancer. Mol Cancer Ther 2014;13:3137-51.

154. Park SM, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev 2008;22:894-907.

155. Hu J, Qiu M, Jiang F, Zhang S, Yang X, et al. MiR-145 regulates cancer stem-like properties and epithelial-to-mesenchymal transition in lung adenocarcinoma-initiating cells. Tumour Biol 2014;35:8953-61.

156. Zhang Z, Liu S, Shi R, Zhao G. miR-27 promotes human gastric cancer cell metastasis by inducing epithelial-to-mesenchymal transition. Cancer Genet 2011;204:486-91.

157. Zhang H, Li M, Han Y, Hong L, Gong T, et al. Down-regulation of miR-27a might reverse multidrug resistance of esophageal squamous cell carcinoma. Dig Dis Sci 2010;55:2545-51.

158. An X, Sarmiento C, Tan T, Zhu H. Regulation of multidrug resistance by microRNAs in anti-cancer therapy. Acta Pharm Sin B 2017;7:38-51.

159. Kitamura K, Seike M, Okano T, Matsuda K, Miyanaga A, et al. MiR-134/487b/655 cluster regulates TGF-β-induced epithelial-mesenchymal transition and drug resistance to gefitinib by targeting MAGI2 in lung adenocarcinoma cells. Mol Cancer Ther 2014;13:444-53.

160. Kokubo Y, Gemma A, Noro R, Seike M, Kataoka K, et al. Reduction of PTEN protein and loss of epidermal growth factor receptor gene mutation in lung cancer with natural resistance to gefitinib (IRESSA). Br J Cancer 2005;92:1711-9.

161. Qian Y, Wang X, Liu Y, Li Y, Colvin RA, et al. Extracellular ATP is internalized by macropinocytosis and induces intracellular ATP increase and drug resistance in cancer cells. Cancer Lett 2014;351:242-51.

162. Pfeiffer T, Schuster S, Bonhoeffer S. Cooperation and competition in the evolution of ATP-producing pathways. Science 2001;292:504-7.

163. Pecqueur C, Oliver L, Oizel K, Lalier L, Vallette FM. Targeting metabolism to induce cell death in cancer cells and cancer stem cells. Int J Cell Biol 2013;2013:805975.

164. Liu Y, Cao Y, Zhang W, Bergmeier S, Qian Y, et al. A small-molecule inhibitor of glucose transporter 1 downregulates glycolysis, induces cell-cycle arrest, and inhibits cancer cell growth in vitro and in vivo. Mol Cancer Ther 2012;11:1672-82.

165. Warburg O. On the origin of cancer cells. Science 1956;123:309-14.

166. Koppenol WH, Bounds PL, Dang CV. Otto Warburg’s contributions to current concepts of cancer metabolism. Nat Rev Cancer 2011;11:325-37.

167. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009;324:1029-33.

168. Zhou Y, Tozzi F, Chen J, Fan F, Xia L, et al. Intracellular ATP levels are a pivotal determinant of chemoresistance in colon cancer cells. Cancer Res 2012;72:304-14.

169. Schneider V, Krieger ML, Bendas G, Jaehde U, Kalayda GV. Contribution of intracellular ATP to cisplatin resistance of tumor cells. J Biol Inorg Chem 2013;18:165-74.

170. Ko YH, Smith BL, Wang Y, Pomper MG, Rini DA, et al. Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to deplete ATP. Biochem Biophys Res Commun 2004;324:269-75.

171. Zhou M, Zhao Y, Ding Y, Liu H, Liu Z, et al. Warburg effect in chemosensitivity: Targeting lactate dehydrogenase-A re-sensitizes Taxol-resistant cancer cells to Taxol. Mol Cancer 2010;9:33.

172. Le A, Cooper CR, Gouw AM, Dinavahi R, Maitra A, et al. Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc Natl Acad Sci 2010;107:2037-42.

173. Qian Y, Wang X, Chen X. Inhibitors of glucose transport and glycolysis as novel anticancer therapeutics. World J Transl Med 2014;3:37.

174. Ganapathy-Kanniappan S, Geschwind JF. Tumor glycolysis as a target for cancer therapy: progress and prospects. Mol Cancer 2013;12:152.

175. Pellegatti P, Raffaghello L, Bianchi G, Piccardi F, Pistoia V, et al. Increased level of extracellular ATP at tumor sites: in vivo imaging with plasma membrane luciferase. PLoS One 2008;3:e2599.

176. Falzoni S, Donvito G, Di Virgilio F. Detecting adenosine triphosphate in the pericellular space. Interface Focus 2013;3:20120101.

177. Michaud M, Martins I, Sukkurwala AQ, Adjemian S, Ma Y, et al. Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science 2011;334:1573-7.

178. Wilhelm K, Ganesan J, Müller T, Dürr C, Grimm M, et al. Graft-versus-host disease is enhanced by extracellular ATP activating P2X7R. Nat Med 2010;16:1434-8.

179. Wang X, Li Y, Qian Y, Cao Y, Shriwas P, et al. Extracellular ATP, as an energy and phosphorylating molecule, induces different types of drug resistances in cancer cells through ATP internalization and intracellular ATP level increase. Oncotarget 2017;8:87860-77.

180. Qian Y, Wang X, Li Y, Cao Y, Chen X. Extracellular ATP a new player in cancer metabolism: NSCLC cells internalize ATP in vitro and in vivo using multiple endocytic mechanisms. Mol Cancer Res 2016;14:1087-96.

181. Di Virgilio F, Sarti AC, Falzoni S, De Marchi E, Adinolfi E. Extracellular ATP and P2 purinergic signalling in the tumour microenvironment. Nat Rev Cancer 2018;18:601-18.

182. Di Virgilio F, Ferrari D, Adinolfi E. P2X(7): a growth-promoting receptor-implications for cancer. Purinergic Signal 2009;5:251-6.

183. Burnstock G, Di Virgilio F. Purinergic signalling and cancer. Purinergic Signal 2013;9:491-540.

184. Vinette V, Placet M, Arguin G, Gendron FP. Multidrug resistance-associated protein 2 expression is upregulated by adenosine 5’-triphosphate in colorectal cancer cells and enhances their survival to chemotherapeutic drugs. PLoS One 2015;10:e0136080.

185. Deli T, Varga N, Ádám A, Kenessey I, Rásó E, et al. Functional genomics of calcium channels in human melanoma cells. Int J Cancer 2007;121:55-65.

186. Limami Y, Pinon A, Leger DY, Pinault E, Delage C, et al. The P2Y2/Src/p38/COX-2 pathway is involved in the resistance to ursolic acid-induced apoptosis in colorectal and prostate cancer cells. Biochimie 2012;94:1754-63.

187. Morrone FB, Oliveira DL, Gamermann P, Stella J, Wofchuk S, et al. In vivo glioblastoma growth is reduced by apyrase activity in a rat glioma model. BMC Cancer 2006;6:226.

188. Elliott MR, Chekeni FB, Trampont PC, Lazarowski ER, Kadl A, et al. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 2009;461:282-6.

189. Galluzzi L, Buqué A, Kepp O, Zitvogel L, Kroemer G. Immunogenic cell death in cancer and infectious disease. Nat Rev Immunol 2017;17:97-111.

190. Ko A, Kanehisa A, Martins I, Senovilla L, Chargari C, et al. Autophagy inhibition radiosensitizes in vitro, yet reduces radioresponses in vivo due to deficient immunogenic signalling. Cell Death Differ 2014;21:92-9.

191. Galluzzi L, Kepp O, Kroemer G. Enlightening the impact of immunogenic cell death in photodynamic cancer therapy. EMBO J 2012;31:1055-7.

192. Ghiringhelli F, Apetoh L, Tesniere A, Aymeric L, Ma Y, et al. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β-dependent adaptive immunity against tumors. Nat Med 2009;15:1170-8.

193. Filippini A, Taffs RE, Sitkovsky MV. Extracellular ATP in T-lymphocyte activation: possible role in effector functions. Proc Natl Acad Sci U S A 1990;87:8267-71.

194. Piccini A, Carta S, Tassi S, Lasiglie D, Fossati G, et al. ATP is released by monocytes stimulated with pathogen-sensing receptor ligands and induces IL-1 and IL-18 secretion in an autocrine way. Proc Natl Acad Sci 2008;105:8067-72.

195. Antonioli L, Pacher P, Vizi ES, Haskó G. CD39 and CD73 in immunity and inflammation. Trends Mol Med 2013;19:355-67.

196. Regateiro FS, Cobbold SP, Waldmann H. CD73 and adenosine generation in the creation of regulatory microenvironments. Clin Exp Immunol 2013;171:1-7.

197. Stagg J, Smyth MJ. Extracellular adenosine triphosphate and adenosine in cancer. Oncogene 2010;29:5346-58.

198. Ohta A. A metabolic immune checkpoint: adenosine in tumor microenvironment. Front Immunol 2016;7:109.

199. Yang H, Ma Y, Chen G, Zhou H, Yamazaki T, et al. Contribution of RIP3 and MLKL to immunogenic cell death signaling in cancer chemotherapy. Oncoimmunology 2016;5:e1149673.

200. Kaiser J. When less is more. Science 2017;355:1144-6.

201. Moriceau G, Hugo W, Hong A, Shi H, Kong X, et al. Tunable-combinatorial mechanisms of acquired resistance limit the efficacy of BRAF/MEK cotargeting but result in melanoma drug addiction. Cancer Cell 2015;27:240-56.

202. Amin AD, Rajan SS, Liang WS, Pongtornpipat P, Groysman MJ, et al. Evidence suggesting that discontinuous dosing of ALK kinase inhibitors may prolong control of ALK+ tumors. Cancer Res 2015;75:2916.

203. Hay N. Reprogramming glucose metabolism in cancer: can it be exploited for cancer therapy? Nat Publ Gr 2016;16:635-49.

204. Zhu A, Lee D, Shim H. Metabolic positron emission tomography imaging in cancer detection and therapy response. Semin Oncol 2011;38:55-69.

205. Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer 2011;11:85-95.

Cancer Drug Resistance
ISSN 2578-532X (Online)
Follow Us


All published articles will preserved here permanently:


All published articles will preserved here permanently: