{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T06:38:51Z","timestamp":1780382331331,"version":"3.54.1"},"reference-count":45,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T00:00:00Z","timestamp":1655683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009950","name":"Ministry of Education","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Small cell lung cancer (SCLC) is a highly aggressive disease with a poor prognosis. Although most patients initially respond to topoisomerase inhibitors, resistance rapidly emerges. The aim, therefore, is to overcome resistance to topoisomerase I (irinotecan) or II (etoposide) inhibitors in SCLCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To identify key factors in the chemoresistance of SCLCs, we established four cell lines resistant to etoposide or an active metabolite of irinotecan, SN\u201038, from SCLC cell lines and evaluated RNA profiles using parental and newly established cell lines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that the drug efflux protein, ATP\u2010binding cassette sub\u2010family B member 1 (ABCB1), was associated with resistance to etoposide, and ATP\u2010binding cassette sub\u2010family G member 2 (ABCG2) was associated with resistance to SN\u201038 by RNA sequencing. The inhibition of ABCB1 or ABCG2 in each resistant cell line induced synergistic apoptotic activity and promoted drug sensitivity in resistant SCLC cells. The ABC transporter inhibitors, elacridar and tariquidar, restored sensitivity to etoposide or SN\u201038 in in vitro and in vivo studies, and promoted apoptotic activity and G2\u2010M arrest in resistant SCLC cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>ABC transporter inhibitors may be a promising therapeutic strategy for the purpose of overcoming resistance to topoisomerase inhibitors in patients with SCLC.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1759-7714.14527","type":"journal-article","created":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T07:49:42Z","timestamp":1655711382000},"page":"2142-2151","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Inhibitors of <scp>ABCB1<\/scp> and <scp>ABCG2<\/scp> overcame resistance to topoisomerase inhibitors in small cell lung cancer"],"prefix":"10.1111","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7342-2026","authenticated-orcid":false,"given":"Miwako","family":"Omori","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine and Oncology Graduate School of Medicine, Nippon Medical School  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4912-4138","authenticated-orcid":false,"given":"Rintaro","family":"Noro","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine and Oncology Graduate School of Medicine, Nippon Medical School  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Seike","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine and Oncology Graduate School of Medicine, Nippon Medical School  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuniko","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine and Oncology Graduate School of Medicine, Nippon Medical School  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Hirao","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine and Oncology Graduate School of Medicine, Nippon Medical School  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Fukuizumi","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine and Oncology Graduate School of Medicine, Nippon Medical School  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsuki","family":"Takano","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine and Oncology Graduate School of Medicine, Nippon Medical School  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2026-9181","authenticated-orcid":false,"given":"Akihiko","family":"Miyanaga","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine and Oncology Graduate School of Medicine, Nippon Medical School  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Gemma","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine and Oncology Graduate School of Medicine, Nippon Medical School  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,20]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"2","article-title":"Cellular and molecular biology of small cell lung cancer: an overview","volume":"5","author":"Karachaliou N","year":"2016","journal-title":"Transl Lung Cancer Res"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20160583"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa003034"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2019.10.021"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.01055"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1809064"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32222-6"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-2958"},{"key":"e_1_2_8_10_1","doi-asserted-by":"crossref","unstructured":"Matsumoto M Seike M Noro R. 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