{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:43:30Z","timestamp":1790711010544,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2016,6,20]],"date-time":"2016-06-20T00:00:00Z","timestamp":1466380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology of Japan","doi-asserted-by":"crossref","award":["25221303"],"award-info":[{"award-number":["25221303"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:p>\n                    Cancer stem cells (\n                    <jats:styled-content style=\"fixed-case\">CSC<\/jats:styled-content>\n                    s) generate transient\u2010amplifying cells and thereby contribute to cancer propagation. A fuller understanding of the biological features of\n                    <jats:styled-content style=\"fixed-case\">CSC<\/jats:styled-content>\n                    s is expected to lead to the development of new anticancer therapies capable of eradicating this life\u2010threatening disease. Cancer stem cells are known to maintain a non\u2010proliferative state and to enter the cell cycle only infrequently. Given that conventional anticancer therapies preferentially target dividing cells,\n                    <jats:styled-content style=\"fixed-case\">CSC<\/jats:styled-content>\n                    s are resistant to such treatments, with those remaining after elimination of bulk cancer cells potentially giving rise to disease relapse and metastasis as they re\u2010enter the cell cycle after a period of latency. Targeting of the switch between quiescence and proliferation in\n                    <jats:styled-content style=\"fixed-case\">CSC<\/jats:styled-content>\n                    s is therefore a potential strategy for preventing the reinitiation of malignancy, underscoring the importance of elucidation of the mechanisms by which these cells are maintained in the quiescent state. The fundamental properties of\n                    <jats:styled-content style=\"fixed-case\">CSC<\/jats:styled-content>\n                    s are thought to be governed cooperatively by internal molecules and cues from the external microenvironment (stem cell niche). Several such intrinsic and extrinsic regulators are responsible for the control of cell cycle progression in\n                    <jats:styled-content style=\"fixed-case\">CSC<\/jats:styled-content>\n                    s. In this review, we address two opposite approaches to the therapeutic targeting of\n                    <jats:styled-content style=\"fixed-case\">CSC<\/jats:styled-content>\n                    s \u2013 wake\u2010up and hibernation therapies \u2013 that either promote or prevent the entry of\n                    <jats:styled-content style=\"fixed-case\">CSC<\/jats:styled-content>\n                    s into the cell cycle, respectively, and we discuss the potential advantages and risks of each strategy.\n                  <\/jats:p>","DOI":"10.1111\/cas.12958","type":"journal-article","created":{"date-parts":[[2016,4,27]],"date-time":"2016-04-27T04:27:30Z","timestamp":1461731250000},"page":"875-881","source":"Crossref","is-referenced-by-count":84,"title":["To wake up cancer stem cells, or to let them sleep, that is the question"],"prefix":"10.1111","volume":"107","author":[{"given":"Shoichiro","family":"Takeishi","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biology Medical Institute of Bioregulation Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichi I.","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology Medical Institute of Bioregulation Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,6,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2014.02.006"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.12817"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2010.06.001"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2015.02.015"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2013.00174"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-08-3532"},{"key":"e_1_2_9_8_1","first-page":"233","article-title":"Arsenic and old myths","volume":"77","author":"Aronson SM","year":"1994","journal-title":"R I Med"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07016"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2882"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0128288"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-13-1040"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3638"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.04.036"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1881"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.01.026"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2014.259"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1621808"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2007.00708.x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15248"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.06.4451"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-0429"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12532"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1607"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1350"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.10.048"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa025406"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-09-3728"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200405203502124"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.8.2478"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-10-4202"},{"key":"e_1_2_9_32_1","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1182\/blood.V83.8.2086.2086","article-title":"A double\u2010blind controlled study of granulocyte colony\u2010stimulating factor started two days before induction chemotherapy in refractory acute myeloid leukemia. 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