{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T14:52:19Z","timestamp":1793371939516,"version":"4.5.0"},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T00:00:00Z","timestamp":1701302400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014106","name":"Stichting STOPhersentumoren.nl","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014106","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>\n                    <jats:italic>BRAF<\/jats:italic>\n                    <jats:sup>V600<\/jats:sup>\n                    \u2010mutated melanoma brain metastases (MBMs) are responsive to BRAF inhibitors, but responses are generally less durable than those of extracranial metastases. We tested the hypothesis that the drug efflux transporters P\u2010glycoprotein (P\u2010gp; ABCB1) and breast cancer resistance protein (BCRP; ABCG2) expressed at the blood\u2013brain barrier (BBB) offer MBMs protection from therapy. We intracranially implanted A375 melanoma cells in wild\u2010type (WT) and\n                    <jats:italic>Abcb1a\/b;Abcg2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, characterized the tumor BBB, analyzed drug levels in plasma and brain lesions after oral vemurafenib administration, and determined the efficacy against brain metastases and subcutaneous lesions. Although contrast\u2010enhanced MRI demonstrated that the integrity of the BBB is disrupted in A375 MBMs, vemurafenib achieved greater antitumor efficacy against MBMs in\n                    <jats:italic>Abcb1a\/b;Abcg2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice compared with WT mice. Concordantly, P\u2010gp and BCRP are expressed in MBM\u2010associated brain endothelium both in patients and in A375 xenografts and expression of these transporters limited vemurafenib penetration into A375 MBMs. Although initially responsive, A375 MBMs rapidly developed therapy resistance, even in\n                    <jats:italic>Abcb1a\/b;Abcg2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, and this was unrelated to pharmacokinetic or target inhibition issues. Taken together, we demonstrate that both intrinsic and acquired resistance can play a role in MBMs.\n                  <\/jats:p>","DOI":"10.1002\/2211-5463.13730","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T00:26:00Z","timestamp":1699835160000},"page":"96-111","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Acquired and intrinsic resistance to vemurafenib in\n                    <scp>\n                      BRAF\n                      <sup>V600E<\/sup>\n                    <\/scp>\n                    \u2010driven melanoma brain metastases"],"prefix":"10.1002","volume":"14","author":[{"given":"Ping","family":"Zhang","sequence":"first","affiliation":[{"name":"Division of Pharmacology The Netherlands Cancer Institute  Amsterdam The Netherlands"},{"name":"Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain\u2010Inspired Science Shandong University  China"},{"name":"Shandong Provincial Key Laboratory of Brain Function Remodeling, Qilu Hospital Shandong University  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3330-1371","authenticated-orcid":false,"given":"Laura Esmee","family":"Kuil","sequence":"additional","affiliation":[{"name":"Division of Pharmacology The Netherlands Cancer Institute  Amsterdam The Netherlands"},{"name":"Division of Psychosocial Sciences and Epidemiology The Netherlands Cancer Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levi Conrad Maria","family":"Buil","sequence":"additional","affiliation":[{"name":"Division of Pharmacology The Netherlands Cancer Institute  Amsterdam The Netherlands"},{"name":"Mouse Cancer Clinic The Netherlands Cancer Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Freriks","sequence":"additional","affiliation":[{"name":"Division of Pharmacology The Netherlands Cancer Institute  Amsterdam The Netherlands"},{"name":"Mouse Cancer Clinic The Netherlands Cancer Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0118-561X","authenticated-orcid":false,"given":"Jos Hendrik","family":"Beijnen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmacology The Netherlands Cancer Institute\/MC Slotervaart Hospital  Amsterdam The Netherlands"},{"name":"Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science Utrecht University  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1037-6269","authenticated-orcid":false,"given":"Olaf","family":"van Tellingen","sequence":"additional","affiliation":[{"name":"Division of Pharmacology The Netherlands Cancer Institute  Amsterdam The Netherlands"},{"name":"Mouse Cancer Clinic The Netherlands Cancer Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2812-991X","authenticated-orcid":false,"given":"Mark Cornelis","family":"de Gooijer","sequence":"additional","affiliation":[{"name":"Division of Pharmacology The Netherlands Cancer Institute  Amsterdam The Netherlands"},{"name":"Faculty of Biology, Medicine and Health University of Manchester  UK"},{"name":"The Christie NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30946"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature00766"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.06.024"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-0776"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-013-0095-2"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-018-0963-x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103782"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60868-X"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2923"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-13-0617"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/1060028016672037"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2017-0642"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30142-6"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30122-X"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60898-4"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70431-X"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30429-1"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp3003144"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.112.192195"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.112.201475"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2017.11.006"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0000000000000162"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.acr.2014.10.001"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2018.05.001"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-17-0600"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2020.100184"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910410419"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-1694"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2010.01.007"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13121"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09626"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6712"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.04.012"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2015.02.002"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2017.06.008"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0933-9"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2010.12.009"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0887-y"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-2062"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13000-016-0506-2"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2938"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00230349"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.5414\/NP300903"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24735"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07208.x"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067583"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2012-3790"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711741105"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-0887"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0000000000000034"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-14-0257"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-3122"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-17-1263"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.50"}],"container-title":["FEBS Open Bio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/2211-5463.13730","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T00:29:32Z","timestamp":1705537772000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/2211-5463.13730"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,30]]},"references-count":55,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/2211-5463.13730"],"URL":"https:\/\/doi.org\/10.1002\/2211-5463.13730","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/2211-5463.13730\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.13730\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.13730\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.13730\/v2\/decision1","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.12.20.521202","asserted-by":"object"}]},"ISSN":["2211-5463","2211-5463"],"issn-type":[{"value":"2211-5463","type":"print"},{"value":"2211-5463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,30]]},"assertion":[{"value":"2023-04-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}