{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:57:15Z","timestamp":1791262635268,"version":"4.1.0"},"reference-count":181,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cancer stem cells (CSCs) are a therapy\u2010refractory subpopulation that drives tumor persistence, recurrence, and metastasis. A defining characteristic of CSCs is their ability to reversibly exit the cell cycle and enter a quiescent state, thereby escaping cytotoxic therapies that primarily target proliferating cells. Although numerous reviews have examined CSC dormancy and quiescence, less attention has been devoted to recently identified regulators and to the molecular events associated with the transition into quiescence. This narrative review consolidates current knowledge on CSC\u2010specific entry regulators, including the pRb\/RBL2\u2013E2F1\/4\u2013GCN5 axis, Fbxw7\u2013c\u2010Myc pathway, PML\u2013PPAR\u03b4\u2013FAO axis, ID1\/ID3\u2013p21 network, JARID1B\u2010mediated G\n                    <jats:sub>0<\/jats:sub>\n                    \u2010like states, CDH1\u2013SIRT5\u2013Cyclin F axis, and AP\u20101\/ETS network, alongside emerging evidence on epigenetic regulation, circadian influences, and immune\u2010mediated signals. We critically evaluate the exhaustion hypothesis, delineate a therapeutic framework that distinguishes between prevention of quiescence entry, elimination of dormant CSCs, and forced reactivation, and identify key knowledge gaps. By integrating recent advances within a structured perspective, this review provides a framework for understanding how CSCs exploit quiescence for survival and therapy resistance and informs strategies to target this resilient population.\n                  <\/jats:p>","DOI":"10.1002\/cam4.72301","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:17:17Z","timestamp":1790054237000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cancer Stem Cell Quiescence: Molecular and Microenvironmental Evidence for an Actively Regulated Adaptive Survival Strategy"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6721-1775","authenticated-orcid":false,"given":"Yasin","family":"Ahmadi","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Science Komar University of Sciences and Technology  Sulaymaniyah Kurdistan Region Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2026-1617","authenticated-orcid":false,"given":"Trefa M.","family":"Abdullah","sequence":"additional","affiliation":[{"name":"Department of Basic Science, College of Pharmacy University of Sulaimani  Sulaymaniyah Kurdistan Region Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9888-7508","authenticated-orcid":false,"given":"Sakhavat","family":"Abolhasani","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences and Health Sarab Faculty of Medical Sciences  Sarab East Azerbaijan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1095-8906","authenticated-orcid":false,"given":"Amin","family":"Jalizi","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences and Health Sarab Faculty of Medical Sciences  Sarab East Azerbaijan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201034395\u20102"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9971"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05372"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0530291100"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2020.100909"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010024\u201001801\u2010y"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.24678"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1417201"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2014.259"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2014.07.001"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.165084"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555\u2010022\u201010073\u2010z"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375\u2010019\u20100490\u20100"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9182"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bneo.2025.100146"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2022.280800"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11287"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201020\u20100378"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.04.036"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.12174.1"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02166"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.15430\/JCP.2014.19.2.89"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929\u2010018\u20100426\u20104"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u201021\u20100010"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388\u2010025\u201003529\u20103"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2025.218097"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201010\u20101499"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015\u2010020\u201010031\u20108"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.107985"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.4161\/23723548.2014.968067"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010024\u201001851\u2010y"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.20517\/2394\u20105079.2022.43"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47680-z"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.125138"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07016"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2014.10.035"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10091295"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.32604\/biocell.2022.016346"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201059503\u2010w"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201058370\u20109"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-3377"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.2174\/0118715206336851241204111721"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2219"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2015.61"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2017.10.001"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/396076"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16741"},{"key":"e_1_2_14_49_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20100323"},{"key":"e_1_2_14_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010019\u20101115\u20101"},{"key":"e_1_2_14_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100854.2006.00420.x"},{"key":"e_1_2_14_52_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.15804"},{"key":"e_1_2_14_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388\u2010022\u201002329\u20103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