{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T09:11:16Z","timestamp":1767863476994,"version":"3.49.0"},"reference-count":17,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,9,2]],"date-time":"2014-09-02T00:00:00Z","timestamp":1409616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Institute of Health","award":["1U54CA143970-01"],"award-info":[{"award-number":["1U54CA143970-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2015,2,15]]},"abstract":"<jats:p>ATP\u2010binding cassette (ABC) drug transporters consuming ATPs for drug efflux is a common mechanism by which clinical cancers develop multidrug resistance (MDR). We hypothesized that MDR phenotypes could be suppressed by administration of \u201cersatzdroges,\u201d nonchemotherapy drugs that are, nevertheless, ABC substrates. We reasoned that, through prolonged activation of the ABC pumps, ersatzdroges will force MDR cells to divert limited resources from proliferation and invasion thus delaying disease progression. We evaluated ABC substrates as ersatzdroge by comparing their effects on proliferation and survival of MDR cell lines (MCF\u20107\/Dox and 8226\/Dox40) with the effects on the drug\u2010sensitive parental lines (MCF\u20107 and 8226\/s, respectively) in glucose\u2010limited condition. The changes in glucose and energy demands were also examined <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. MCF\u20107\/Dox showed higher ATP demand and susceptibility to glucose resource limitation. Ersatzdroges significantly decreased proliferation of MCF\u20107\/Dox when the culture media contained physiological glucose concentrations (1.0 g\/L) or less, but had no effect on MCF\u20107. Similar evidence was obtained from 8226\/Dox40 and 8226\/s comparison. <jats:italic>In vivo<\/jats:italic> 18F\u2010FDG\u2010PET imaging demonstrated that glucose uptake was increased by systemic administration of an ersatzdroge in tumors composed of MDR. These results suggest that administration of ersatzdroges, by increasing the metabolic cost of resistance, can suppress proliferation of drug\u2010resistance phenotypes. This provides a novel and relatively simple application model of evolution\u2010based strategy, which can exploit the cost of resistance to delay proliferation of drug\u2010resistant cancer phenotypes. Furthermore, suggested is the potential of ersatzdroges to identify tumors or regions of tumors that express the MDR phenotype.<\/jats:p>","DOI":"10.1002\/ijc.29158","type":"journal-article","created":{"date-parts":[[2014,8,23]],"date-time":"2014-08-23T08:10:58Z","timestamp":1408781458000},"source":"Crossref","is-referenced-by-count":44,"title":["Sweat but no gain: Inhibiting proliferation of multidrug resistant cancer cells with \u201cersatzdroges\u201d"],"prefix":"10.1002","volume":"136","author":[{"given":"Yoonseok","family":"Kam","sequence":"first","affiliation":[{"name":"Department of Cancer Imaging and Metabolism H. Lee Moffitt Cancer Center and Research Institute Tampa FL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuhin","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Cancer Imaging and Metabolism H. Lee Moffitt Cancer Center and Research Institute Tampa FL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haibin","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Cancer Imaging and Metabolism H. Lee Moffitt Cancer Center and Research Institute Tampa FL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parastou","family":"Foroutan","sequence":"additional","affiliation":[{"name":"Department of Cancer Imaging and Metabolism H. Lee Moffitt Cancer Center and Research Institute Tampa FL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Epifanio","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Department of Cancer Imaging and Metabolism H. Lee Moffitt Cancer Center and Research Institute Tampa FL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Cancer Imaging and Metabolism H. Lee Moffitt Cancer Center and Research Institute Tampa FL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Minton","sequence":"additional","affiliation":[{"name":"Department of Women's Oncology H. Lee Moffitt Cancer Center and Research Institute Tampa FL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Gillies","sequence":"additional","affiliation":[{"name":"Department of Cancer Imaging and Metabolism H. Lee Moffitt Cancer Center and Research Institute Tampa FL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Gatenby","sequence":"additional","affiliation":[{"name":"Department of Cancer Imaging and Metabolism H. 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