{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:47:31Z","timestamp":1791586051744,"version":"4.3.4"},"reference-count":51,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"497","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R44TR001326"],"award-info":[{"award-number":["R44TR001326"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007013","name":"Hoffman-La Roche","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2019,6,19]]},"abstract":"<jats:p>An in vitro multi-organ system evaluates the efficacy and potential off-target toxicities of anticancer parent drugs and metabolites.<\/jats:p>","DOI":"10.1126\/scitranslmed.aav1386","type":"journal-article","created":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T19:14:21Z","timestamp":1560971661000},"source":"Crossref","is-referenced-by-count":194,"title":["Multi-organ system for the evaluation of efficacy and off-target toxicity of anticancer therapeutics"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9550-7458","authenticated-orcid":true,"given":"Christopher W.","family":"McAleer","sequence":"first","affiliation":[{"name":"Hesperos Inc., 3259 Progress Drive, Room 158, Orlando, FL 32826, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2333-7576","authenticated-orcid":true,"given":"Christopher J.","family":"Long","sequence":"additional","affiliation":[{"name":"Hesperos Inc., 3259 Progress Drive, Room 158, Orlando, FL 32826, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1328-958X","authenticated-orcid":true,"given":"Daniel","family":"Elbrecht","sequence":"additional","affiliation":[{"name":"Hesperos Inc., 3259 Progress Drive, Room 158, Orlando, FL 32826, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor","family":"Sasserath","sequence":"additional","affiliation":[{"name":"Hesperos Inc., 3259 Progress Drive, Room 158, Orlando, FL 32826, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1840-2940","authenticated-orcid":true,"given":"L. Richard","family":"Bridges","sequence":"additional","affiliation":[{"name":"Hesperos Inc., 3259 Progress Drive, Room 158, Orlando, FL 32826, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2591-2351","authenticated-orcid":true,"given":"John W.","family":"Rumsey","sequence":"additional","affiliation":[{"name":"Hesperos Inc., 3259 Progress Drive, Room 158, Orlando, FL 32826, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candace","family":"Martin","sequence":"additional","affiliation":[{"name":"NanoScience Technology Center, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, FL 32826, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Schnepper","sequence":"additional","affiliation":[{"name":"NanoScience Technology Center, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, FL 32826, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0236-5962","authenticated-orcid":true,"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"NanoScience Technology Center, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, FL 32826, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz","family":"Schuler","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann\u2013La Roche Ltd., Grenzacherstrasse 124, CH-4070 Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3164-3300","authenticated-orcid":true,"given":"Adrian B.","family":"Roth","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann\u2013La Roche Ltd., Grenzacherstrasse 124, CH-4070 Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Funk","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann\u2013La Roche Ltd., Grenzacherstrasse 124, CH-4070 Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4662-317X","authenticated-orcid":true,"given":"Michael L.","family":"Shuler","sequence":"additional","affiliation":[{"name":"Hesperos Inc., 3259 Progress Drive, Room 158, Orlando, FL 32826, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1621-3006","authenticated-orcid":true,"given":"James J.","family":"Hickman","sequence":"additional","affiliation":[{"name":"Hesperos Inc., 3259 Progress Drive, Room 158, Orlando, FL 32826, USA."},{"name":"NanoScience Technology Center, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, FL 32826, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.082041"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-6296(02)00126-1"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/1740774515625964"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4309"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1039\/C4IB00292J"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.07.062"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep20030"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201970049"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-22749-0"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200104053441401"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2408149"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.2147\/TCRM.S1527"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2012.12.012"},{"key":"e_1_3_2_15_2","first-page":"65","article-title":"Diclofenac toxicity to hepatocytes: A role for drug metabolism in cell toxicity","volume":"288","author":"Bort R.","year":"1999","unstructured":"R. Bort, X. Ponsoda, R. Jover, M. J. G\u00f3mez-Lech\u00f3n, J. V. Castell, Diclofenac toxicity to hepatocytes: A role for drug metabolism in cell toxicity. J. Pharmacol. Exp. Ther. 288, 65\u201372 (1999).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/bcr1639"},{"key":"e_1_3_2_17_2","first-page":"4618","article-title":"Effects of biologically active metabolites of tamoxifen on the proliferation kinetics of MCF-7 human breast cancer cells in vitro","volume":"43","author":"Reddel R. R.","year":"1983","unstructured":"R. R. Reddel, L. C. Murphy, R. L. Sutherland, Effects of biologically active metabolites of tamoxifen on the proliferation kinetics of MCF-7 human breast cancer cells in vitro. Cancer Res. 43, 4618\u20134624 (1983).","journal-title":"Cancer Res."},{"key":"e_1_3_2_18_2","first-page":"317","article-title":"Tamoxifen and metabolites in MCF7 cells: Correlation between binding to estrogen receptor and inhibition of cell growth","volume":"42","author":"Coezy E.","year":"1982","unstructured":"E. Coezy, J.-L. Borgna, H. Rochefort, Tamoxifen and metabolites in MCF7 cells: Correlation between binding to estrogen receptor and inhibition of cell growth. Cancer Res. 42, 317\u2013323 (1982).","journal-title":"Cancer Res."},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1984.113"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(93)90061-8"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djp440"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0078768"},{"key":"e_1_3_2_23_2","first-page":"877","article-title":"The antiestrogen tamoxifen blocks the delayed rectifier potassium current, IKr, in rabbit ventricular myocytes","volume":"287","author":"Liu X.-K.","year":"1998","unstructured":"X.-K. Liu, A. Katchman, S. N. Ebert, R. L. Woosley, The antiestrogen tamoxifen blocks the delayed rectifier potassium current, IKr, in rabbit ventricular myocytes. J. Pharmacol. Exp. Ther. 287, 877\u2013883 (1998).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.105.008615"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7254.2007.00562.x"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1995.13.8.2039"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/bit.25989"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1039\/b917763a"},{"key":"e_1_3_2_29_2","first-page":"935","article-title":"Approval summary for imatinib mesylate capsules in the treatment of chronic myelogenous leukemia","volume":"8","author":"Cohen M. H.","year":"2002","unstructured":"M. H. Cohen, G. Williams, J. R. Johnson, J. Duan, J. Gobburu, A. Rahman, K. Benson, J. Leighton, S. K. Kim, R. Wood, M. Rothmann, G. Chen, K. M. U, A. M. Staten, R. Pazdur, Approval summary for imatinib mesylate capsules in the treatment of chronic myelogenous leukemia. Clin. Cancer Res. 8, 935\u2013942 (2002).","journal-title":"Clin. Cancer Res."},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aet464"},{"key":"e_1_3_2_31_2","first-page":"610","article-title":"Repurposing drugs in oncology (ReDO)\u2014Diclofenac as an anti-cancer agent","volume":"10","author":"Pantziarka P.","year":"2016","unstructured":"P. Pantziarka, V. Sukhatme, G. Bouche, L. Meheus, V. P. Sukhatme, Repurposing drugs in oncology (ReDO)\u2014Diclofenac as an anti-cancer agent. Ecancermedicalscience 10, 610 (2016).","journal-title":"Ecancermedicalscience"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1177\/0192623311419524"},{"key":"e_1_3_2_33_2","first-page":"315","article-title":"Principal long-term adverse effects of imatinib in patients with chronic myeloid leukemia in chronic phase","volume":"4","author":"Mughal T. I.","year":"2010","unstructured":"T. I. Mughal, A. Schrieber, Principal long-term adverse effects of imatinib in patients with chronic myeloid leukemia in chronic phase. Biologics 4, 315\u2013323 (2010).","journal-title":"Biologics"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-008X(03)00368-5"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.104.003095"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.2063"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.4817939"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2017.05.023"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep08883"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac401910d"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfw227"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1039\/C7LC00210F"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-013-2457-6"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0248-4900(02)00018-7"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2015.04.035"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)71171-4"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.12.022"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00612.2014"},{"key":"e_1_3_2_49_2","first-page":"e51866","article-title":"Utilization of microscale silicon cantilevers to assess cellular contractile function in vitro","volume":"2014","author":"Smith A. S. T.","year":"2014","unstructured":"A. S. T. Smith, C. J. Long, C. W. McAleer, N. Bobbitt, B. Srinivasan, J. J. Hickman, Utilization of microscale silicon cantilevers to assess cellular contractile function in vitro. J. Vis. Exp. 2014, e51866 (2014).","journal-title":"J. Vis. Exp."},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011042"},{"key":"e_1_3_2_51_2","doi-asserted-by":"crossref","unstructured":"C. Oleaga G. Legters L. R. Bridges L. Kumanchik C. Martin Y. Cai M. Schnepper C. W. McAleer C. J. Long J. J. Hickman in Stem Cell-Derived Models in Toxicology Methods in Pharmacology and Toxicology M. Clements L. Roquemore Eds. (Humana Press 2017) pp. 229\u2013246.","DOI":"10.1007\/978-1-4939-6661-5_12"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1126\/scitranslmed.aav1386","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.aav1386","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T13:41:47Z","timestamp":1705412507000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.aav1386"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,19]]},"references-count":51,"journal-issue":{"issue":"497","published-print":{"date-parts":[[2019,6,19]]}},"alternative-id":["10.1126\/scitranslmed.aav1386"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.aav1386","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,19]]},"article-number":"eaav1386"}}