{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:57:18Z","timestamp":1793159838114,"version":"4.5.0"},"reference-count":127,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Exp Metastasis"],"published-print":{"date-parts":[[2018,4]]},"DOI":"10.1007\/s10585-018-9903-0","type":"journal-article","created":{"date-parts":[[2018,5,24]],"date-time":"2018-05-24T06:17:52Z","timestamp":1527142672000},"page":"309-318","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":562,"title":["The challenge of drug\u00a0resistance in cancer treatment: a current overview"],"prefix":"10.1007","volume":"35","author":[{"given":"Michail","family":"Nikolaou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasia","family":"Pavlopoulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandros G.","family":"Georgakilas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5236-7961","authenticated-orcid":false,"given":"Efthymios","family":"Kyrodimos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,5,24]]},"reference":[{"key":"9903_CR1","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1146\/annurev.med.53.082901.103929","volume":"53","author":"MM Gottesman","year":"2002","unstructured":"Gottesman MM (2002) Mechanisms of cancer drug resistance. Annu Rev Med 53:615\u2013627. https:\/\/doi.org\/10.1146\/annurev.med.53.082901.103929","journal-title":"Annu Rev Med"},{"key":"9903_CR2","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-017-2374-9","volume-title":"Multiple drug resistance in cancer 2: molecular, cellular and clinical aspects","author":"M Clynes","year":"1998","unstructured":"Clynes M (1998) Multiple drug resistance in cancer 2: molecular, cellular and clinical aspects. Kluwer Academic Publishers, Dodrecht"},{"issue":"17","key":"9903_CR3","doi-asserted-by":"publisher","first-page":"3427","DOI":"10.1158\/0008-5472.CAN-15-0308","volume":"75","author":"JM Ebos","year":"2015","unstructured":"Ebos JM (2015) Prodding the beast: assessing the Impact of treatment-induced metastasis. Cancer Res 75(17):3427\u20133435. https:\/\/doi.org\/10.1158\/0008-5472.CAN-15-0308","journal-title":"Cancer Res"},{"key":"9903_CR4","doi-asserted-by":"publisher","first-page":"108","DOI":"10.3389\/fphys.2014.00108","volume":"5","author":"KS Sherlach","year":"2014","unstructured":"Sherlach KS, Roepe PD (2014) Drug resistance associated membrane proteins. Front Physiol 5:108. https:\/\/doi.org\/10.3389\/fphys.2014.00108","journal-title":"Front Physiol"},{"issue":"3","key":"9903_CR5","doi-asserted-by":"publisher","first-page":"339","DOI":"10.15171\/apb.2017.041","volume":"7","author":"B Mansoori","year":"2017","unstructured":"Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B (2017) The different mechanisms of cancer drug resistance: a brief review. Adv Pharm Bull 7(3):339\u2013348. https:\/\/doi.org\/10.15171\/apb.2017.041","journal-title":"Adv Pharm Bull"},{"issue":"31","key":"9903_CR6","first-page":"18","volume":"6","author":"MM Gottesman","year":"2006","unstructured":"Gottesman MM, Ludwig J, Xia D, Szakacs G (2006) Defeating drug resistance in cancer. Discov Med 6(31):18\u201323","journal-title":"Discov Med"},{"issue":"2","key":"9903_CR7","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/j.canlet.2016.07.018","volume":"380","author":"A Pavlopoulou","year":"2016","unstructured":"Pavlopoulou A, Oktay Y, Vougas K, Louka M, Vorgias CE, Georgakilas AG (2016) Determinants of resistance to chemotherapy and ionizing radiation in breast cancer stem cells. Cancer Lett 380(2):485\u2013493. https:\/\/doi.org\/10.1016\/j.canlet.2016.07.018","journal-title":"Cancer Lett"},{"issue":"3","key":"9903_CR8","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.ccr.2008.08.001","volume":"14","author":"Y Shaked","year":"2008","unstructured":"Shaked Y, Henke E, Roodhart JM, Mancuso P, Langenberg MH, Colleoni M, Daenen LG, Man S, Xu P, Emmenegger U, Tang T, Zhu Z, Witte L, Strieter RM, Bertolini F, Voest EE, Benezra R, Kerbel RS (2008) Rapid chemotherapy-induced acute endothelial progenitor cell mobilization: implications for antiangiogenic drugs as chemosensitizing agents. Cancer Cell 14(3):263\u2013273. https:\/\/doi.org\/10.1016\/j.ccr.2008.08.001","journal-title":"Cancer Cell"},{"issue":"3","key":"9903_CR9","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.3390\/cancers6031769","volume":"6","author":"G Housman","year":"2014","unstructured":"Housman G, Byler S, Heerboth S, Lapinska K, Longacre M, Snyder N, Sarkar S (2014) Drug resistance in cancer: an overview. Cancers 6(3):1769\u20131792. https:\/\/doi.org\/10.3390\/cancers6031769","journal-title":"Cancers"},{"issue":"4","key":"9903_CR10","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/j.maturitas.2013.09.008","volume":"76","author":"WD Joo","year":"2013","unstructured":"Joo WD, Visintin I, Mor G (2013) Targeted cancer therapy\u2014are the days of systemic chemotherapy numbered? Maturitas 76(4):308\u2013314. https:\/\/doi.org\/10.1016\/j.maturitas.2013.09.008","journal-title":"Maturitas"},{"issue":"1","key":"9903_CR11","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1111\/j.1365-2125.2006.02713.x","volume":"62","author":"S Kummar","year":"2006","unstructured":"Kummar S, Gutierrez M, Doroshow JH, Murgo AJ (2006) Drug development in oncology: classical cytotoxics and molecularly targeted agents. Br J Clin Pharmacol 62(1):15\u201326. https:\/\/doi.org\/10.1111\/j.1365-2125.2006.02713.x","journal-title":"Br J Clin Pharmacol"},{"issue":"6","key":"9903_CR12","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1016\/j.molonc.2014.05.004","volume":"8","author":"FH Groenendijk","year":"2014","unstructured":"Groenendijk FH, Bernards R (2014) Drug resistance to targeted therapies: deja vu all over again. Mol Oncol 8(6):1067\u20131083. https:\/\/doi.org\/10.1016\/j.molonc.2014.05.004","journal-title":"Mol Oncol"},{"issue":"3","key":"9903_CR13","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1038\/nrd1984","volume":"5","author":"G Szakacs","year":"2006","unstructured":"Szakacs G, Paterson JK, Ludwig JA, Booth-Genthe C, Gottesman MM (2006) Targeting multidrug resistance in cancer. Nat Rev Drug Discov 5(3):219\u2013234. https:\/\/doi.org\/10.1038\/nrd1984","journal-title":"Nat Rev Drug Discov"},{"issue":"5","key":"9903_CR14","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1038\/87912","volume":"7","author":"TW Synold","year":"2001","unstructured":"Synold TW, Dussault I, Forman BM (2001) The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nat Med 7(5):584\u2013590. https:\/\/doi.org\/10.1038\/87912","journal-title":"Nat Med"},{"issue":"3","key":"9903_CR15","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1096\/fj.00-0223com","volume":"15","author":"YY Liu","year":"2001","unstructured":"Liu YY, Han TY, Giuliano AE, Cabot MC (2001) Ceramide glycosylation potentiates cellular multidrug resistance. FASEB J 15(3):719\u2013730. https:\/\/doi.org\/10.1096\/fj.00-0223com","journal-title":"FASEB J"},{"key":"9903_CR16","doi-asserted-by":"publisher","first-page":"157","DOI":"10.3389\/fgene.2015.00157","volume":"6","author":"A Torgovnick","year":"2015","unstructured":"Torgovnick A, Schumacher B (2015) DNA repair mechanisms in cancer development and therapy. Front Genet 6:157. https:\/\/doi.org\/10.3389\/fgene.2015.00157","journal-title":"Front Genet"},{"issue":"6","key":"9903_CR17","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1016\/0092-8674(93)90719-7","volume":"74","author":"SW Lowe","year":"1993","unstructured":"Lowe SW, Ruley HE, Jacks T, Housman DE (1993) p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74(6):957\u2013967","journal-title":"Cell"},{"issue":"1\u20132","key":"9903_CR18","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.drup.2007.02.002","volume":"10","author":"T Fojo","year":"2007","unstructured":"Fojo T (2007) Multiple paths to a drug resistance phenotype: mutations, translocations, deletions and amplification of coding genes or promoter regions, epigenetic changes and microRNAs. Drug Resist Updates 10 (1\u20132):59\u201367. https:\/\/doi.org\/10.1016\/j.drup.2007.02.002","journal-title":"Drug Resist Updates"},{"issue":"7381","key":"9903_CR19","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1038\/nature10762","volume":"481","author":"M Greaves","year":"2012","unstructured":"Greaves M, Maley CC (2012) Clonal evolution in cancer. Nature 481(7381):306\u2013313. https:\/\/doi.org\/10.1038\/nature10762","journal-title":"Nature"},{"issue":"4260","key":"9903_CR20","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1126\/science.959840","volume":"194","author":"PC Nowell","year":"1976","unstructured":"Nowell PC (1976) The clonal evolution of tumor cell populations. Science 194(4260):23\u201328","journal-title":"Science"},{"issue":"11\u201312","key":"9903_CR21","first-page":"1727","volume":"63","author":"JH Goldie","year":"1979","unstructured":"Goldie JH, Coldman AJ (1979) A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep 63(11\u201312):1727\u20131733","journal-title":"Cancer Treat Rep"},{"issue":"3","key":"9903_CR22","first-page":"222","volume":"12","author":"JH Goldie","year":"1985","unstructured":"Goldie JH, Coldman AJ (1985) Genetic instability in the development of drug resistance. Semin Oncol 12(3):222\u2013230","journal-title":"Semin Oncol"},{"issue":"3\u20134","key":"9903_CR23","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1007\/BF02459682","volume":"48","author":"AJ Coldman","year":"1986","unstructured":"Coldman AJ, Goldie JH (1986) A stochastic model for the origin and treatment of tumors containing drug-resistant cells. Bull Math Biol 48(3\u20134):279\u2013292","journal-title":"Bull Math Biol"},{"issue":"2","key":"9903_CR24","doi-asserted-by":"publisher","first-page":"157","DOI":"10.3109\/07853899509031953","volume":"27","author":"JR Woodhouse","year":"1995","unstructured":"Woodhouse JR, Ferry DR (1995) The genetic basis of resistance to cancer chemotherapy. Ann Med 27(2):157\u2013167","journal-title":"Ann Med"},{"issue":"2","key":"9903_CR25","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/s002850000053","volume":"42","author":"WP Angerer","year":"2001","unstructured":"Angerer WP (2001) An explicit representation of the Luria-Delbruck distribution. J Math Biol 42(2):145\u2013174","journal-title":"J Math Biol"},{"issue":"2","key":"9903_CR26","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.mbs.2005.07.003","volume":"197","author":"A Dewanji","year":"2005","unstructured":"Dewanji A, Luebeck EG, Moolgavkar SH (2005) A generalized Luria-Delbruck model. Math Biosci 197(2):140\u2013152. https:\/\/doi.org\/10.1016\/j.mbs.2005.07.003","journal-title":"Math Biosci"},{"issue":"4","key":"9903_CR27","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/S0022-5193(03)00117-6","volume":"223","author":"SA Frank","year":"2003","unstructured":"Frank SA (2003) Somatic mosaicism and cancer: inference based on a conditional Luria-Delbruck distribution. J Theor Biol 223(4):405\u2013412","journal-title":"J Theor Biol"},{"issue":"4","key":"9903_CR28","doi-asserted-by":"publisher","first-page":"2209","DOI":"10.1534\/genetics.107.078915","volume":"177","author":"H Haeno","year":"2007","unstructured":"Haeno H, Iwasa Y, Michor F (2007) The evolution of two mutations during clonal expansion. Genetics 177(4):2209\u20132221. https:\/\/doi.org\/10.1534\/genetics.107.078915","journal-title":"Genetics"},{"issue":"4","key":"9903_CR29","doi-asserted-by":"publisher","first-page":"2557","DOI":"10.1534\/genetics.105.049791","volume":"172","author":"Y Iwasa","year":"2006","unstructured":"Iwasa Y, Nowak MA, Michor F (2006) Evolution of resistance during clonal expansion. Genetics 172(4):2557\u20132566. https:\/\/doi.org\/10.1534\/genetics.105.049791","journal-title":"Genetics"},{"issue":"3","key":"9903_CR30","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/j.jtbi.2005.01.014","volume":"235","author":"NL Komarova","year":"2005","unstructured":"Komarova NL, Mironov V (2005) On the role of endothelial progenitor cells in tumor neovascularization. J Theor Biol 235(3):338\u2013349. https:\/\/doi.org\/10.1016\/j.jtbi.2005.01.014","journal-title":"J Theor Biol"},{"issue":"27","key":"9903_CR31","doi-asserted-by":"publisher","first-page":"9714","DOI":"10.1073\/pnas.0501870102","volume":"102","author":"NL Komarova","year":"2005","unstructured":"Komarova NL, Wodarz D (2005) Drug resistance in cancer: principles of emergence and prevention. Proc Natl Acad Sci USA 102(27):9714\u20139719. https:\/\/doi.org\/10.1073\/pnas.0501870102","journal-title":"Proc Natl Acad Sci USA"},{"issue":"21","key":"9903_CR32","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1093\/jnci\/87.21.1593","volume":"87","author":"L Beketic-Oreskovic","year":"1995","unstructured":"Beketic-Oreskovic L, Duran GE, Chen G, Dumontet C, Sikic BI (1995) Decreased mutation rate for cellular resistance to doxorubicin and suppression of mdr1 gene activation by the cyclosporin PSC 833. J Natl Cancer Inst 87(21):1593\u20131602","journal-title":"J Natl Cancer Inst"},{"issue":"18","key":"9903_CR33","first-page":"4980","volume":"54","author":"G Chen","year":"1994","unstructured":"Chen G, Jaffrezou JP, Fleming WH, Duran GE, Sikic BI (1994) Prevalence of multidrug resistance related to activation of the mdr1 gene in human sarcoma mutants derived by single-step doxorubicin selection. Cancer Res 54(18):4980\u20134987","journal-title":"Cancer Res"},{"issue":"5","key":"9903_CR34","first-page":"1091","volume":"56","author":"C Dumontet","year":"1996","unstructured":"Dumontet C, Duran GE, Steger KA, Beketic-Oreskovic L, Sikic BI (1996) Resistance mechanisms in human sarcoma mutants derived by single-step exposure to paclitaxel (Taxol). Cancer Res 56(5):1091\u20131097","journal-title":"Cancer Res"},{"issue":"15","key":"9903_CR35","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1093\/jnci\/86.15.1152","volume":"86","author":"JP Jaffrezou","year":"1994","unstructured":"Jaffrezou JP, Chen G, Duran GE, Kuhl JS, Sikic BI (1994) Mutation rates and mechanisms of resistance to etoposide determined from fluctuation analysis. J Natl Cancer Inst 86(15):1152\u20131158","journal-title":"J Natl Cancer Inst"},{"issue":"20","key":"9903_CR36","doi-asserted-by":"publisher","first-page":"9388","DOI":"10.1158\/0008-5472.CAN-04-4133","volume":"65","author":"KG Chen","year":"2005","unstructured":"Chen KG, Wang YC, Schaner ME, Francisco B, Duran GE, Juric D, Huff LM, Padilla-Nash H, Ried T, Fojo T, Sikic BI (2005) Genetic and epigenetic modeling of the origins of multidrug-resistant cells in a human sarcoma cell line. Cancer Res 65(20):9388\u20139397. https:\/\/doi.org\/10.1158\/0008-5472.CAN-04-4133","journal-title":"Cancer Res"},{"issue":"22","key":"9903_CR37","first-page":"5086","volume":"57","author":"Y Matsumoto","year":"1997","unstructured":"Matsumoto Y, Takano H, Fojo T (1997) Cellular adaptation to drug exposure: evolution of the drug-resistant phenotype. Cancer Res 57(22):5086\u20135092","journal-title":"Cancer Res"},{"issue":"10","key":"9903_CR38","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1056\/NEJMoa1113205","volume":"366","author":"M Gerlinger","year":"2012","unstructured":"Gerlinger M, Rowan AJ, Horswell S, Math M, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. New Engl J Med 366(10):883\u2013892. https:\/\/doi.org\/10.1056\/NEJMoa1113205","journal-title":"New Engl J Med"},{"issue":"8","key":"9903_CR39","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1016\/j.bcp.2011.12.008","volume":"83","author":"AJ Lee","year":"2012","unstructured":"Lee AJ, Swanton C (2012) Tumour heterogeneity and drug resistance: personalising cancer medicine through functional genomics. Biochem Pharmacol 83(8):1013\u20131020. https:\/\/doi.org\/10.1016\/j.bcp.2011.12.008","journal-title":"Biochem Pharmacol"},{"issue":"19","key":"9903_CR40","doi-asserted-by":"publisher","first-page":"4875","DOI":"10.1158\/0008-5472.CAN-12-2217","volume":"72","author":"C Swanton","year":"2012","unstructured":"Swanton C (2012) Intratumor heterogeneity: evolution through space and time. Cancer Res 72(19):4875\u20134882. https:\/\/doi.org\/10.1158\/0008-5472.CAN-12-2217","journal-title":"Cancer Res"},{"key":"9903_CR41","first-page":"397","volume":"24","author":"FW Alt","year":"1992","unstructured":"Alt FW, Kellems RE, Bertino JR, Schimke RT (1992) Selective multiplication of dihydrofolate reductase genes in methotrexate-resistant variants of cultured murine cells. 1978. Biotechnology 24:397\u2013410","journal-title":"Biotechnology"},{"issue":"4","key":"9903_CR42","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1002\/gcc.20300","volume":"45","author":"YC Wang","year":"2006","unstructured":"Wang YC, Juric D, Francisco B, Yu RX, Duran GE, Chen GK, Chen X, Sikic BI (2006) Regional activation of chromosomal arm 7q with and without gene amplification in taxane-selected human ovarian cancer cell lines. Genes Chromosomes Cancer 45(4):365\u2013374. https:\/\/doi.org\/10.1002\/gcc.20300","journal-title":"Genes Chromosomes Cancer"},{"issue":"9","key":"9903_CR43","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1158\/0008-5472.CAN-11-3909","volume":"72","author":"D Matei","year":"2012","unstructured":"Matei D, Fang F, Shen C, Schilder J, Arnold A, Zeng Y, Berry WA, Huang T, Nephew KP (2012) Epigenetic resensitization to platinum in ovarian cancer. Cancer Res 72(9):2197\u20132205. https:\/\/doi.org\/10.1158\/0008-5472.CAN-11-3909","journal-title":"Cancer Res"},{"key":"9903_CR44","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1007\/978-1-4419-9967-2_14","volume":"754","author":"C Balch","year":"2013","unstructured":"Balch C, Nephew KP (2013) Epigenetic targeting therapies to overcome chemotherapy resistance. Adv Exp Med Biol 754:285\u2013311. https:\/\/doi.org\/10.1007\/978-1-4419-9967-2_14","journal-title":"Adv Exp Med Biol"},{"issue":"1\u20132","key":"9903_CR45","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.drup.2012.01.008","volume":"15","author":"RH Wilting","year":"2012","unstructured":"Wilting RH, Dannenberg JH (2012) Epigenetic mechanisms in tumorigenesis, tumor cell heterogeneity and drug resistance. Drug Resist Updates 15 (1\u20132):21\u201338. https:\/\/doi.org\/10.1016\/j.drup.2012.01.008","journal-title":"Drug Resist Updates"},{"issue":"42","key":"9903_CR46","doi-asserted-by":"publisher","first-page":"4567","DOI":"10.1038\/onc.2011.611","volume":"31","author":"C Zeller","year":"2012","unstructured":"Zeller C, Dai W, Steele NL, Siddiq A, Walley AJ, Wilhelm-Benartzi CS, Rizzo S, van der Zee A, Plumb JA, Brown R (2012) Candidate DNA methylation drivers of acquired cisplatin resistance in ovarian cancer identified by methylome and expression profiling. Oncogene 31(42):4567\u20134576. https:\/\/doi.org\/10.1038\/onc.2011.611","journal-title":"Oncogene"},{"issue":"10","key":"9903_CR47","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1101\/gad.2037511","volume":"25","author":"AM Deaton","year":"2011","unstructured":"Deaton AM, Bird A (2011) CpG islands and the regulation of transcription. Genes Dev 25(10):1010\u20131022. https:\/\/doi.org\/10.1101\/gad.2037511","journal-title":"Genes Dev"},{"issue":"22","key":"9903_CR48","doi-asserted-by":"publisher","first-page":"5201","DOI":"10.1182\/blood-2012-01-401687","volume":"119","author":"T Bhatla","year":"2012","unstructured":"Bhatla T, Wang J, Morrison DJ, Raetz EA, Burke MJ, Brown P, Carroll WL (2012) Epigenetic reprogramming reverses the relapse-specific gene expression signature and restores chemosensitivity in childhood B-lymphoblastic leukemia. Blood 119(22):5201\u20135210. https:\/\/doi.org\/10.1182\/blood-2012-01-401687","journal-title":"Blood"},{"key":"9903_CR49","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s13148-017-0319-5","volume":"9","author":"ME Issa","year":"2017","unstructured":"Issa ME, Takhsha FS, Chirumamilla CS, Perez-Novo C, Vanden Berghe W, Cuendet M (2017) Epigenetic strategies to reverse drug resistance in heterogeneous multiple myeloma. Clin Epigenetics 9:17. https:\/\/doi.org\/10.1186\/s13148-017-0319-5","journal-title":"Clin Epigenetics"},{"issue":"1","key":"9903_CR50","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1007\/s10555-007-9050-6","volume":"26","author":"Y Huang","year":"2007","unstructured":"Huang Y (2007) Pharmacogenetics\/genomics of membrane transporters in cancer chemotherapy. Cancer Metastasis Rev 26(1):183\u2013201. https:\/\/doi.org\/10.1007\/s10555-007-9050-6","journal-title":"Cancer Metastasis Rev"},{"issue":"6","key":"9903_CR51","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1023\/A:1012866803188","volume":"33","author":"MM Gottesman","year":"2001","unstructured":"Gottesman MM, Ambudkar SV (2001) Overview: ABC transporters and human disease. J Bioenerg Biomembr 33(6):453\u2013458","journal-title":"J Bioenerg Biomembr"},{"issue":"1","key":"9903_CR52","doi-asserted-by":"publisher","first-page":"27","DOI":"10.2174\/1567201043480036","volume":"1","author":"H Glavinas","year":"2004","unstructured":"Glavinas H, Krajcsi P, Cserepes J, Sarkadi B (2004) The role of ABC transporters in drug resistance, metabolism and toxicity. Curr Drug Deliv 1(1):27\u201342","journal-title":"Curr Drug Delivery"},{"issue":"2","key":"9903_CR53","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1182\/blood.V79.2.473.473","volume":"79","author":"L Campos","year":"1992","unstructured":"Campos L, Guyotat D, Archimbaud E, Calmard-Oriol P, Tsuruo T, Troncy J, Treille D, Fiere D (1992) Clinical significance of multidrug resistance P-glycoprotein expression on acute nonlymphoblastic leukemia cells at diagnosis. Blood 79(2):473\u2013476","journal-title":"Blood"},{"issue":"4","key":"9903_CR54","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1200\/JCO.1989.7.4.415","volume":"7","author":"WS Dalton","year":"1989","unstructured":"Dalton WS, Grogan TM, Meltzer PS, Scheper RJ, Durie BG, Taylor CW, Miller TP, Salmon SE (1989) Drug-resistance in multiple myeloma and non-Hodgkin\u2019s lymphoma: detection of P-glycoprotein and potential circumvention by addition of verapamil to chemotherapy. J Clin Oncol 7(4):415\u2013424. https:\/\/doi.org\/10.1200\/JCO.1989.7.4.415","journal-title":"J Clin Oncol"},{"issue":"3","key":"9903_CR55","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1182\/blood.V78.3.586.586","volume":"78","author":"JP Marie","year":"1991","unstructured":"Marie JP, Zittoun R, Sikic BI (1991) Multidrug resistance (mdr1) gene expression in adult acute leukemias: correlations with treatment outcome and in vitro drug sensitivity. Blood 78(3):586\u2013592","journal-title":"Blood"},{"issue":"1","key":"9903_CR56","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1200\/JCO.1991.9.1.17","volume":"9","author":"TP Miller","year":"1991","unstructured":"Miller TP, Grogan TM, Dalton WS, Spier CM, Scheper RJ, Salmon SE (1991) P-glycoprotein expression in malignant lymphoma and reversal of clinical drug resistance with chemotherapy plus high-dose verapamil. J Clin Oncol 9(1):17\u201324. https:\/\/doi.org\/10.1200\/JCO.1991.9.1.17","journal-title":"J Clin Oncol"},{"issue":"47","key":"9903_CR57","doi-asserted-by":"publisher","first-page":"7468","DOI":"10.1038\/sj.onc.1206948","volume":"22","author":"SV Ambudkar","year":"2003","unstructured":"Ambudkar SV, Kimchi-Sarfaty C, Sauna ZE, Gottesman MM (2003) P-glycoprotein: from genomics to mechanism. Oncogene 22(47):7468\u20137485. https:\/\/doi.org\/10.1038\/sj.onc.1206948","journal-title":"Oncogene"},{"issue":"11","key":"9903_CR58","doi-asserted-by":"publisher","first-page":"3674","DOI":"10.1200\/JCO.1998.16.11.3674","volume":"16","author":"DM Bradshaw","year":"1998","unstructured":"Bradshaw DM, Arceci RJ (1998) Clinical relevance of transmembrane drug efflux as a mechanism of multidrug resistance. J Clin Oncol 16(11):3674\u20133690. https:\/\/doi.org\/10.1200\/JCO.1998.16.11.3674","journal-title":"J Clin Oncol"},{"issue":"6 Suppl 7","key":"9903_CR59","doi-asserted-by":"publisher","first-page":"S9S15","DOI":"10.1053\/j.seminoncol.2005.09.009","volume":"32","author":"R Clarke","year":"2005","unstructured":"Clarke R, Leonessa F, Trock B (2005) Multidrug resistance\/P-glycoprotein and breast cancer: review and meta-analysis. Semin Oncol 32(6 Suppl 7):S9\u2013S15. https:\/\/doi.org\/10.1053\/j.seminoncol.2005.09.009","journal-title":"Semin Oncol"},{"issue":"7","key":"9903_CR60","doi-asserted-by":"publisher","first-page":"1940","DOI":"10.1182\/blood-2003-07-2490","volume":"104","author":"D Mahadevan","year":"2004","unstructured":"Mahadevan D, List AF (2004) Targeting the multidrug resistance-1 transporter in AML: molecular regulation and therapeutic strategies. Blood 104(7):1940\u20131951. https:\/\/doi.org\/10.1182\/blood-2003-07-2490","journal-title":"Blood"},{"issue":"2","key":"9903_CR61","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/S0889-8588(18)30099-6","volume":"9","author":"GA Fisher","year":"1995","unstructured":"Fisher GA, Sikic BI (1995) Clinical studies with modulators of multidrug resistance. Hematol\/Oncol Clin N Am 9(2):363\u2013382","journal-title":"Hematol\/Oncol Clin N Am"},{"issue":"9","key":"9903_CR62","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1200\/JCO.1993.11.9.1629","volume":"11","author":"BI Sikic","year":"1993","unstructured":"Sikic BI (1993) Modulation of multidrug resistance: at the threshold. J Clin Oncol 11(9):1629\u20131635. https:\/\/doi.org\/10.1200\/JCO.1993.11.9.1629","journal-title":"J Clin Oncol"},{"issue":"4 Suppl 5","key":"9903_CR63","first-page":"40","volume":"34","author":"BI Sikic","year":"1997","unstructured":"Sikic BI (1997) Pharmacologic approaches to reversing multidrug resistance. Semin Hematol 34(4 Suppl 5):40\u201347","journal-title":"Semin Hematol"},{"issue":"5","key":"9903_CR64","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1038\/bjc.1989.141","volume":"59","author":"G Capranico","year":"1989","unstructured":"Capranico G, De Isabella P, Castelli C, Supino R, Parmiani G, Zunino F (1989) P-glycoprotein gene amplification and expression in multidrug-resistant murine P388 and B16 cell lines. Br J Cancer 59(5):682\u2013685","journal-title":"Br J Cancer"},{"issue":"1\u20132","key":"9903_CR65","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.drup.2012.01.005","volume":"15","author":"S Shukla","year":"2012","unstructured":"Shukla S, Chen ZS, Ambudkar SV (2012) Tyrosine kinase inhibitors as modulators of ABC transporter-mediated drug resistance. Drug Resist Updates 15 (1\u20132):70\u201380. https:\/\/doi.org\/10.1016\/j.drup.2012.01.005","journal-title":"Drug Resist Updates"},{"issue":"1","key":"9903_CR66","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s10555-007-9041-7","volume":"26","author":"XB Chang","year":"2007","unstructured":"Chang XB (2007) A molecular understanding of ATP-dependent solute transport by multidrug resistance-associated protein MRP1. Cancer Metastasis Rev 26(1):15\u201337. https:\/\/doi.org\/10.1007\/s10555-007-9041-7","journal-title":"Cancer Metastasis Rev"},{"issue":"5","key":"9903_CR67","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1124\/mol.62.5.1160","volume":"62","author":"D Burg","year":"2002","unstructured":"Burg D, Wielinga P, Zelcer N, Saeki T, Mulder GJ, Borst P (2002) Inhibition of the multidrug resistance protein 1 (MRP1) by peptidomimetic glutathione-conjugate analogs. Mol Pharmacol 62(5):1160\u20131166","journal-title":"Mol Pharmacol"},{"issue":"17","key":"9903_CR68","doi-asserted-by":"crossref","first-page":"10073","DOI":"10.1016\/S0021-9258(19)38781-2","volume":"265","author":"YN Chen","year":"1990","unstructured":"Chen YN, Mickley LA, Schwartz AM, Acton EM, Hwang JL, Fojo AT (1990) Characterization of adriamycin-resistant human breast cancer cells which display overexpression of a novel resistance-related membrane protein. J Biol Chem 265(17):10073\u201310080","journal-title":"J Biol Chem"},{"issue":"1","key":"9903_CR69","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s10555-007-9042-6","volume":"26","author":"RW Robey","year":"2007","unstructured":"Robey RW, Polgar O, Deeken J, To KW, Bates SE (2007) ABCG2: determining its relevance in clinical drug resistance. Cancer Metastasis Rev 26(1):39\u201357. https:\/\/doi.org\/10.1007\/s10555-007-9042-6","journal-title":"Cancer Metastasis Rev"},{"issue":"6","key":"9903_CR70","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1023\/A:1012879205914","volume":"33","author":"SE Bates","year":"2001","unstructured":"Bates SE, Robey R, Miyake K, Rao K, Ross DD, Litman T (2001) The role of half-transporters in multidrug resistance. J Bioenerg Biomembr 33(6):503\u2013511","journal-title":"J Bioenerg Biomembr"},{"issue":"5","key":"9903_CR71","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1093\/jnci\/91.5.429","volume":"91","author":"DD Ross","year":"1999","unstructured":"Ross DD, Yang W, Abruzzo LV, Dalton WS, Schneider E, Lage H, Dietel M, Greenberger L, Cole SP, Doyle LA (1999) Atypical multidrug resistance: breast cancer resistance protein messenger RNA expression in mitoxantrone-selected cell lines. J Natl Cancer Inst 91(5):429\u2013433","journal-title":"J Natl Cancer Inst"},{"key":"9903_CR72","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s12943-015-0362-9","volume":"14","author":"D Westover","year":"2015","unstructured":"Westover D, Ling X, Lam H, Welch J, Jin C, Gongora C, Del Rio M, Wani M, Li F (2015) FL118, a novel camptothecin derivative, is insensitive to ABCG2 expression and shows improved efficacy in comparison with irinotecan in colon and lung cancer models with ABCG2-induced resistance. Mol Cancer 14:92. https:\/\/doi.org\/10.1186\/s12943-015-0362-9","journal-title":"Mol Cancer"},{"issue":"3","key":"9903_CR73","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1200\/JCO.1999.17.3.1061","volume":"17","author":"C Dumontet","year":"1999","unstructured":"Dumontet C, Sikic BI (1999) Mechanisms of action of and resistance to antitubulin agents: microtubule dynamics, drug transport, and cell death. J Clin Oncol 17(3):1061\u20131070. https:\/\/doi.org\/10.1200\/JCO.1999.17.3.1061","journal-title":"J Clin Oncol"},{"issue":"47","key":"9903_CR74","doi-asserted-by":"publisher","first-page":"7280","DOI":"10.1038\/sj.onc.1206934","volume":"22","author":"GA Orr","year":"2003","unstructured":"Orr GA, Verdier-Pinard P, McDaid H, Horwitz SB (2003) Mechanisms of Taxol resistance related to microtubules. Oncogene 22(47):7280\u20137295. https:\/\/doi.org\/10.1038\/sj.onc.1206934","journal-title":"Oncogene"},{"issue":"12","key":"9903_CR75","doi-asserted-by":"publisher","first-page":"2001","DOI":"10.1158\/1535-7163.MCT-05-0244","volume":"4","author":"P Seve","year":"2005","unstructured":"Seve P, Mackey J, Isaac S, Tredan O, Souquet PJ, Perol M, Lai R, Voloch A, Dumontet C (2005) Class III beta-tubulin expression in tumor cells predicts response and outcome in patients with non-small cell lung cancer receiving paclitaxel. Mol Cancer Ther 4(12):2001\u20132007. https:\/\/doi.org\/10.1158\/1535-7163.MCT-05-0244","journal-title":"Mol Cancer Ther"},{"issue":"1","key":"9903_CR76","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2174\/1568009033333754","volume":"3","author":"RZ Yusuf","year":"2003","unstructured":"Yusuf RZ, Duan Z, Lamendola DE, Penson RT, Seiden MV (2003) Paclitaxel resistance: molecular mechanisms and pharmacologic manipulation. Curr Cancer Drug Targets 3(1):1\u201319","journal-title":"Curr Cancer Drug Targets"},{"issue":"23","key":"9903_CR77","doi-asserted-by":"publisher","first-page":"8315","DOI":"10.1073\/pnas.0408974102","volume":"102","author":"R Rouzier","year":"2005","unstructured":"Rouzier R, Rajan R, Wagner P, Hess KR, Gold DL, Stec J, Ayers M, Ross JS, Zhang P, Buchholz TA, Kuerer H, Green M, Arun B, Hortobagyi GN, Symmans WF, Pusztai L (2005) Microtubule-associated protein tau: a marker of paclitaxel sensitivity in breast cancer. Proc Natl Acad Sci USA 102(23):8315\u20138320. https:\/\/doi.org\/10.1073\/pnas.0408974102","journal-title":"Proc Natl Acad Sci USA"},{"issue":"9","key":"9903_CR78","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.4161\/cc.4.9.2038","volume":"4","author":"P Wagner","year":"2005","unstructured":"Wagner P, Wang B, Clark E, Lee H, Rouzier R, Pusztai L (2005) Microtubule Associated Protein (MAP)-Tau: a novel mediator of paclitaxel sensitivity in vitro and in vivo. Cell Cycle 4(9):1149\u20131152. https:\/\/doi.org\/10.4161\/cc.4.9.2038","journal-title":"Cell Cycle"},{"issue":"16","key":"9903_CR79","doi-asserted-by":"publisher","first-page":"5565","DOI":"10.1073\/pnas.84.16.5565","volume":"84","author":"T Andoh","year":"1987","unstructured":"Andoh T, Ishii K, Suzuki Y, Ikegami Y, Kusunoki Y, Takemoto Y, Okada K (1987) Characterization of a mammalian mutant with a camptothecin-resistant DNA topoisomerase I. Proc Natl Acad Sci USA 84(16):5565\u20135569","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"9903_CR80","first-page":"58","volume":"49","author":"AM Deffie","year":"1989","unstructured":"Deffie AM, Batra JK, Goldenberg GJ (1989) Direct correlation between DNA topoisomerase II activity and cytotoxicity in adriamycin-sensitive and -resistant P388 leukemia cell lines. Cancer Res 49(1):58\u201362","journal-title":"Cancer Res"},{"issue":"7","key":"9903_CR81","first-page":"1848","volume":"52","author":"A Tanizawa","year":"1992","unstructured":"Tanizawa A, Pommier Y (1992) Topoisomerase I alteration in a camptothecin-resistant cell line derived from Chinese hamster DC3F cells in culture. Cancer Res 52(7):1848\u20131854","journal-title":"Cancer Res"},{"issue":"6","key":"9903_CR82","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1054\/drup.1999.0110","volume":"2","author":"WT Beck","year":"1999","unstructured":"Beck WT, Morgan SE, Mo YY, Bhat UG (1999) Tumor cell resistance to DNA topoisomerase II inhibitors: new developments. Drug Resist Updates 2(6):382\u2013389. https:\/\/doi.org\/10.1054\/drup.1999.0110","journal-title":"Drug Resist Updates"},{"issue":"12","key":"9903_CR83","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.1093\/annonc\/mdf337","volume":"13","author":"Y Xu","year":"2002","unstructured":"Xu Y, Villalona-Calero MA (2002) Irinotecan: mechanisms of tumor resistance and novel strategies for modulating its activity. Ann Oncol 13(12):1841\u20131851","journal-title":"Ann Oncol"},{"issue":"8","key":"9903_CR84","doi-asserted-by":"publisher","first-page":"999","DOI":"10.2217\/fon.12.86","volume":"8","author":"MR Lackner","year":"2012","unstructured":"Lackner MR, Wilson TR, Settleman J (2012) Mechanisms of acquired resistance to targeted cancer therapies. Future Oncol 8(8):999\u20131014. https:\/\/doi.org\/10.2217\/fon.12.86","journal-title":"Future Oncol"},{"issue":"7","key":"9903_CR85","doi-asserted-by":"publisher","first-page":"2242","DOI":"10.1182\/blood-2007-03-066936","volume":"110","author":"T O\u2019Hare","year":"2007","unstructured":"O\u2019Hare T, Eide CA, Deininger MW (2007) Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia. Blood 110(7):2242\u20132249. https:\/\/doi.org\/10.1182\/blood-2007-03-066936","journal-title":"Blood"},{"issue":"4","key":"9903_CR86","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/nrd1691","volume":"4","author":"D Wang","year":"2005","unstructured":"Wang D, Lippard SJ (2005) Cellular processing of platinum anticancer drugs. Nat Rev Drug Discov 4(4):307\u2013320. https:\/\/doi.org\/10.1038\/nrd1691","journal-title":"Nat Rev Drug Discov"},{"issue":"8","key":"9903_CR87","doi-asserted-by":"publisher","first-page":"354","DOI":"10.5414\/CPP40354","volume":"40","author":"B Kaina","year":"2002","unstructured":"Kaina B, Christmann M (2002) DNA repair in resistance to alkylating anticancer drugs. Int J Clin Pharmacol Ther 40(8):354\u2013367","journal-title":"Int J Clin Pharmacol Ther"},{"issue":"12","key":"9903_CR88","doi-asserted-by":"publisher","first-page":"1818","DOI":"10.1093\/annonc\/mdl300","volume":"17","author":"P Ceppi","year":"2006","unstructured":"Ceppi P, Volante M, Novello S, Rapa I, Danenberg KD, Danenberg PV, Cambieri A, Selvaggi G, Saviozzi S, Calogero R, Papotti M, Scagliotti GV (2006) ERCC1 and RRM1 gene expressions but not EGFR are predictive of shorter survival in advanced non-small-cell lung cancer treated with cisplatin and gemcitabine. Ann Oncol 17(12):1818\u20131825. https:\/\/doi.org\/10.1093\/annonc\/mdl300","journal-title":"Ann Oncol"},{"issue":"47","key":"9903_CR89","doi-asserted-by":"publisher","first-page":"7265","DOI":"10.1038\/sj.onc.1206933","volume":"22","author":"ZH Siddik","year":"2003","unstructured":"Siddik ZH (2003) Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 22(47):7265\u20137279. https:\/\/doi.org\/10.1038\/sj.onc.1206933","journal-title":"Oncogene"},{"issue":"4","key":"9903_CR90","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1038\/nrc1319","volume":"4","author":"SL Gerson","year":"2004","unstructured":"Gerson SL (2004) MGMT: its role in cancer aetiology and cancer therapeutics. Nat Rev Cancer 4(4):296\u2013307. https:\/\/doi.org\/10.1038\/nrc1319","journal-title":"Nat Rev Cancer"},{"issue":"6423","key":"9903_CR91","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1038\/362847a0","volume":"362","author":"SW Lowe","year":"1993","unstructured":"Lowe SW, Schmitt EM, Smith SW, Osborne BA, Jacks T (1993) p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 362(6423):847\u2013849. https:\/\/doi.org\/10.1038\/362847a0","journal-title":"Nature"},{"issue":"6423","key":"9903_CR92","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1038\/362849a0","volume":"362","author":"AR Clarke","year":"1993","unstructured":"Clarke AR, Purdie CA, Harrison DJ, Morris RG, Bird CC, Hooper ML, Wyllie AH (1993) Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature 362(6423):849\u2013852. https:\/\/doi.org\/10.1038\/362849a0","journal-title":"Nature"},{"issue":"22","key":"9903_CR93","first-page":"5824","volume":"54","author":"S Fan","year":"1994","unstructured":"Fan S, el-Deiry WS, Bae I, Freeman J, Jondle D, Bhatia K, Fornace AJ Jr, Magrath I, Kohn KW, O\u2019Connor PM (1994) p53 gene mutations are associated with decreased sensitivity of human lymphoma cells to DNA damaging agents. Cancer Res 54(22):5824\u20135830","journal-title":"Cancer Res"},{"key":"9903_CR94","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.ctrv.2016.07.001","volume":"49","author":"A Carnero","year":"2016","unstructured":"Carnero A, Garcia-Mayea Y, Mir C, Lorente J, Rubio IT, LLeonart ME (2016) The cancer stem-cell signaling network and resistance to therapy. Cancer Treat Rev 49:25\u201336. https:\/\/doi.org\/10.1016\/j.ctrv.2016.07.001","journal-title":"Cancer Treat Rev"},{"issue":"8","key":"9903_CR95","first-page":"1117","volume":"62","author":"I Tannock","year":"1978","unstructured":"Tannock I (1978) Cell kinetics and chemotherapy: a critical review. Cancer Treat Rep 62(8):1117\u20131133","journal-title":"Cancer Treat Rep"},{"issue":"2","key":"9903_CR96","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/bjc.1968.34","volume":"22","author":"IF Tannock","year":"1968","unstructured":"Tannock IF (1968) The relation between cell proliferation and the vascular system in a transplanted mouse mammary tumour. Br J Cancer 22(2):258\u2013273","journal-title":"Br J Cancer"},{"issue":"1","key":"9903_CR97","first-page":"31","volume":"12","author":"DG Hirst","year":"1979","unstructured":"Hirst DG, Denekamp J (1979) Tumour cell proliferation in relation to the vasculature. Cell Tissue Kinetics 12(1):31\u201342","journal-title":"Cell Tissue Kinetics"},{"issue":"1","key":"9903_CR98","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/S0360-3016(02)02938-3","volume":"54","author":"AS Ljungkvist","year":"2002","unstructured":"Ljungkvist AS, Bussink J, Rijken PF, Kaanders JH, van der Kogel AJ, Denekamp J (2002) Vascular architecture, hypoxia, and proliferation in first-generation xenografts of human head-and-neck squamous cell carcinomas. Int J Radiat Oncol Biol Phys 54(1):215\u2013228","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"38","key":"9903_CR99","doi-asserted-by":"publisher","first-page":"4319","DOI":"10.1038\/sj.onc.1203782","volume":"19","author":"LA Hazlehurst","year":"2000","unstructured":"Hazlehurst LA, Damiano JS, Buyuksal I, Pledger WJ, Dalton WS (2000) Adhesion to fibronectin via beta1 integrins regulates p27kip1 levels and contributes to cell adhesion mediated drug resistance (CAM-DR). Oncogene 19(38):4319\u20134327. https:\/\/doi.org\/10.1038\/sj.onc.1203782","journal-title":"Oncogene"},{"issue":"1","key":"9903_CR100","first-page":"69","volume":"1","author":"KH Shain","year":"2001","unstructured":"Shain KH, Dalton WS (2001) Cell adhesion is a key determinant in de novo multidrug resistance (MDR): new targets for the prevention of acquired MDR. Mol Cancer Ther 1(1):69\u201378","journal-title":"Mol Cancer Ther"},{"issue":"3","key":"9903_CR101","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1074\/jbc.270.3.1230","volume":"270","author":"GL Wang","year":"1995","unstructured":"Wang GL, Semenza GL (1995) Purification and characterization of hypoxia-inducible factor 1. J Biol Chem 270(3):1230\u20131237","journal-title":"J Biol Chem"},{"issue":"7092","key":"9903_CR102","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1038\/nature04871","volume":"441","author":"J Pouyssegur","year":"2006","unstructured":"Pouyssegur J, Dayan F, Mazure NM (2006) Hypoxia signalling in cancer and approaches to enforce tumour regression. Nature 441(7092):437\u2013443. https:\/\/doi.org\/10.1038\/nature04871","journal-title":"Nature"},{"issue":"16","key":"9903_CR103","doi-asserted-by":"publisher","first-page":"5978","DOI":"10.1073\/pnas.83.16.5978","volume":"83","author":"GC Rice","year":"1986","unstructured":"Rice GC, Hoy C, Schimke RT (1986) Transient hypoxia enhances the frequency of dihydrofolate reductase gene amplification in Chinese hamster ovary cells. Proc Natl Acad Sci USA 83(16):5978\u20135982","journal-title":"Proc Natl Acad Sci USA"},{"issue":"24","key":"9903_CR104","doi-asserted-by":"publisher","first-page":"9261","DOI":"10.1073\/pnas.84.24.9261","volume":"84","author":"GC Rice","year":"1987","unstructured":"Rice GC, Ling V, Schimke RT (1987) Frequencies of independent and simultaneous selection of Chinese hamster cells for methotrexate and doxorubicin (adriamycin) resistance. Proc Natl Acad Sci USA 84(24):9261\u20139264","journal-title":"Proc Natl Acad Sci USA"},{"issue":"12","key":"9903_CR105","first-page":"3387","volume":"62","author":"KM Comerford","year":"2002","unstructured":"Comerford KM, Wallace TJ, Karhausen J, Louis NA, Montalto MC, Colgan SP (2002) Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene. Cancer Res 62(12):3387\u20133394","journal-title":"Cancer Res"},{"issue":"2","key":"9903_CR106","first-page":"181","volume":"2","author":"KA Kennedy","year":"1987","unstructured":"Kennedy KA (1987) Hypoxic cells as specific drug targets for chemotherapy. Anti-Cancer Drug Des 2(2):181\u2013194","journal-title":"Anti-Cancer Drug Des"},{"issue":"7","key":"9903_CR107","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1038\/sj.bjc.6690455","volume":"80","author":"N Raghunand","year":"1999","unstructured":"Raghunand N, He X, van Sluis R, Mahoney B, Baggett B, Taylor CW, Paine-Murrieta G, Roe D, Bhujwalla ZM, Gillies RJ (1999) Enhancement of chemotherapy by manipulation of tumour pH. Br J Cancer 80(7):1005\u20131011. https:\/\/doi.org\/10.1038\/sj.bjc.6690455","journal-title":"Br J Cancer"},{"issue":"7","key":"9903_CR108","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1016\/S0006-2952(03)00468-4","volume":"66","author":"N Raghunand","year":"2003","unstructured":"Raghunand N, Mahoney BP, Gillies RJ (2003) Tumor acidity, ion trapping and chemotherapeutics. II. pH-dependent partition coefficients predict importance of ion trapping on pharmacokinetics of weakly basic chemotherapeutic agents. Biochem Pharmacol 66(7):1219\u20131229","journal-title":"Biochem Pharmacol"},{"issue":"1","key":"9903_CR109","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1002\/1097-0215(20010101)91:1<120::AID-IJC1021>3.0.CO;2-Y","volume":"91","author":"DS Cowan","year":"2001","unstructured":"Cowan DS, Tannock IF (2001) Factors that influence the penetration of methotrexate through solid tissue. Intl J Cancer 91(1):120\u2013125","journal-title":"Intl J Cancer"},{"key":"9903_CR110","volume-title":"The cell: a molecular approach","author":"GM Cooper","year":"2000","unstructured":"Cooper GM (2000) The cell: a molecular approach, 2nd\u00a0edn. Sinauer Associates, Boston University, Sunderland (MA)","edition":"2"},{"issue":"2","key":"9903_CR111","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/S0889-8588(18)30101-1","volume":"9","author":"CP Spears","year":"1995","unstructured":"Spears CP (1995) Clinical resistance to antimetabolites. Hematol\/Oncol Clin N Am 9(2):397\u2013413","journal-title":"Hematol\/Oncol Clin N Am"},{"issue":"15","key":"9903_CR112","doi-asserted-by":"publisher","first-page":"8971","DOI":"10.1074\/jbc.273.15.8971","volume":"273","author":"VA Kickhoefer","year":"1998","unstructured":"Kickhoefer VA, Rajavel KS, Scheffer GL, Dalton WS, Scheper RJ, Rome LH (1998) Vaults are up-regulated in multidrug-resistant cancer cell lines. J Biol Chem 273(15):8971\u20138974","journal-title":"J Biol Chem"},{"issue":"6","key":"9903_CR113","doi-asserted-by":"crossref","first-page":"2464","DOI":"10.1182\/blood.V87.6.2464.bloodjournal8762464","volume":"87","author":"AF List","year":"1996","unstructured":"List AF, Spier CS, Grogan TM, Johnson C, Roe DJ, Greer JP, Wolff SN, Broxterman HJ, Scheffer GL, Scheper RJ, Dalton WS (1996) Overexpression of the major vault transporter protein lung-resistance protein predicts treatment outcome in acute myeloid leukemia. Blood 87(6):2464\u20132469","journal-title":"Blood"},{"issue":"38","key":"9903_CR114","first-page":"109","volume":"233","author":"CD Steuart","year":"1971","unstructured":"Steuart CD, Burke PJ (1971) Cytidine deaminase and the development of resistance to arabinosyl cytosine. Nature 233(38):109\u2013110","journal-title":"Nature"},{"issue":"6","key":"9903_CR115","doi-asserted-by":"publisher","first-page":"823","DOI":"10.7326\/0003-4819-99-6-823","volume":"99","author":"RW Carlson","year":"1983","unstructured":"Carlson RW, Sikic BI (1983) Continuous infusion or bolus injection in cancer chemotherapy. Ann Internal Med 99(6):823\u2013833","journal-title":"Ann Internal Med"},{"issue":"Suppl 4","key":"9903_CR116","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1093\/annonc\/5.suppl_4.S25","volume":"5","author":"J Cassidy","year":"1994","unstructured":"Cassidy J (1994) Chemotherapy administration: doses, infusions and choice of schedule. Ann Oncol 5(Suppl 4):25\u201329 (discussion 29\u201330)","journal-title":"Ann Oncol"},{"issue":"2","key":"9903_CR117","first-page":"233","volume":"16","author":"M Marangolo","year":"2006","unstructured":"Marangolo M, Bengala C, Conte PF, Danova M, Pronzato P, Rosti G, Sagrada P (2006) Dose and outcome: the hurdle of neutropenia (Review). Oncol Rep 16(2):233\u2013248","journal-title":"Oncol Rep"},{"issue":"1","key":"9903_CR118","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s10456-008-9092-6","volume":"11","author":"D Ribatti","year":"2008","unstructured":"Ribatti D (2008) Judah Folkman, a pioneer in the study of angiogenesis. Angiogenesis 11(1):3\u201310. https:\/\/doi.org\/10.1007\/s10456-008-9092-6","journal-title":"Angiogenesis"},{"issue":"9","key":"9903_CR119","doi-asserted-by":"publisher","first-page":"2804","DOI":"10.1158\/1078-0432.CCR-06-1941","volume":"13","author":"AH Kyle","year":"2007","unstructured":"Kyle AH, Huxham LA, Yeoman DM, Minchinton AI (2007) Limited tissue penetration of taxanes: a mechanism for resistance in solid tumors. Clin Cancer Res 13(9):2804\u20132810. https:\/\/doi.org\/10.1158\/1078-0432.CCR-06-1941","journal-title":"Clin Cancer Res"},{"issue":"8","key":"9903_CR120","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/nrc1893","volume":"6","author":"AI Minchinton","year":"2006","unstructured":"Minchinton AI, Tannock IF (2006) Drug penetration in solid tumours. Nat Rev Cancer 6(8):583\u2013592. https:\/\/doi.org\/10.1038\/nrc1893","journal-title":"Nat Rev Cancer"},{"issue":"20","key":"9903_CR121","doi-asserted-by":"publisher","first-page":"6350","DOI":"10.1158\/0008-5472.CAN-11-2025","volume":"71","author":"S Matsumoto","year":"2011","unstructured":"Matsumoto S, Batra S, Saito K, Yasui H, Choudhuri R, Gadisetti C, Subramanian S, Devasahayam N, Munasinghe JP, Mitchell JB, Krishna MC (2011) Antiangiogenic agent sunitinib transiently increases tumor oxygenation and suppresses cycling hypoxia. Cancer Res 71(20):6350\u20136359. https:\/\/doi.org\/10.1158\/0008-5472.CAN-11-2025","journal-title":"Cancer Res"},{"issue":"2","key":"9903_CR122","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1073\/pnas.86.2.695","volume":"86","author":"C Cordon-Cardo","year":"1989","unstructured":"Cordon-Cardo C, O\u2019Brien JP, Casals D, Rittman-Grauer L, Biedler JL, Melamed MR, Bertino JR (1989) Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. Proc Natl Acad Sci USA 86(2):695\u2013698","journal-title":"Proc Natl Acad Sci USA"},{"issue":"4","key":"9903_CR123","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/0092-8674(94)90212-7","volume":"77","author":"AH Schinkel","year":"1994","unstructured":"Schinkel AH, Smit JJ, van Tellingen O, Beijnen JH, Wagenaar E, van Deemter L, Mol CA, van der Valk MA, Robanus-Maandag EC, te Riele HP et al (1994) Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 77(4):491\u2013502","journal-title":"Cell"},{"key":"9903_CR124","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.semcancer.2015.09.002","volume":"35","author":"S Benzekry","year":"2015","unstructured":"Benzekry S, Pasquier E, Barbolosi D, Lacarelle B, Barlesi F, Andre N, Ciccolini J (2015) Metronomic reloaded: theoretical models bringing chemotherapy into the era of precision medicine. Semin Cancer Biol 35:53\u201361. https:\/\/doi.org\/10.1016\/j.semcancer.2015.09.002","journal-title":"Semin Cancer Biol"},{"issue":"8","key":"9903_CR125","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1038\/nrclinonc.2010.82","volume":"7","author":"E Pasquier","year":"2010","unstructured":"Pasquier E, Kavallaris M, Andre N (2010) Metronomic chemotherapy: new rationale for new directions. Nat Rev Clin Oncol 7(8):455\u2013465. https:\/\/doi.org\/10.1038\/nrclinonc.2010.82","journal-title":"Nat Rev Clin Oncol"},{"issue":"4","key":"9903_CR126","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1124\/dmd.113.056176","volume":"42","author":"R Callaghan","year":"2014","unstructured":"Callaghan R, Luk F, Bebawy M (2014) Inhibition of the multidrug resistance P-glycoprotein: time for a change of strategy? Drug Metabol Dispos 42(4):623\u2013631. https:\/\/doi.org\/10.1124\/dmd.113.056176","journal-title":"Drug Metabol Dispos"},{"issue":"D1","key":"9903_CR127","doi-asserted-by":"publisher","first-page":"D362D368","DOI":"10.1093\/nar\/gkw937","volume":"45","author":"D Szklarczyk","year":"2017","unstructured":"Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M, Santos A, Doncheva NT, Roth A, Bork P, Jensen LJ, von Mering C (2017) The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res 45(D1):D362\u2013D368. https:\/\/doi.org\/10.1093\/nar\/gkw937","journal-title":"Nucleic Acids Res"}],"container-title":["Clinical &amp; Experimental Metastasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s10585-018-9903-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10585-018-9903-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10585-018-9903-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T23:16:39Z","timestamp":1661296599000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s10585-018-9903-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4]]},"references-count":127,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["9903"],"URL":"https:\/\/doi.org\/10.1007\/s10585-018-9903-0","relation":{},"ISSN":["0262-0898","1573-7276"],"issn-type":[{"value":"0262-0898","type":"print"},{"value":"1573-7276","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4]]},"assertion":[{"value":"30 April 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 May 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 May 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}