{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T23:57:38Z","timestamp":1779926258881,"version":"3.53.1"},"reference-count":207,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Science and Culture, Japan","award":["25K10718"],"award-info":[{"award-number":["25K10718"]}]},{"name":"Kyowa-Kirin Co., Ltd."},{"name":"Daiichi-Sankyo Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>(1) Background: All-trans retinoic acid (ATRA) has transformed the treatment of acute promyelocytic leukemia (APL) by inducing terminal myeloid differentiation. However, its efficacy in non-APL acute myeloid leukemia (AML) is limited. Exploring combination strategies that enhance ATRA-induced differentiation may broaden its therapeutic potential. (2) Methods: A literature search of PubMed using the keywords \u201cATRA,\u201d \u201cmyeloid,\u201d and \u201cdifferentiation inducer or enhancer\u201d identified more than 500 published papers as of November 2025. Pre-clinical and clinical studies were reviewed, with a focus on mechanisms, combination partners, and translational relevance. (3) Results: Clinical evidence confirms that ATRA combined with arsenic trioxide or epigenetic modulators achieves high remission rates in APL and selected AML subtypes. Pre-clinical studies show synergistic differentiation effects when ATRA is combined with CDK and kinase inhibitors, nucleotide synthesis inhibitors, DNA-damaging agents, Bcl-2\/MDM2 inhibitors, proteasome inhibitors, cytokines, glycosylation modifiers, natural products, and antibiotic-derived compounds. Mechanistically, these combinations modulate key signaling pathways (MAPK, Akt, JAK\/STAT), stabilize RAR\u03b1, remodel chromatin, and perturb nucleotide metabolism. Although translation to non-APL AML remains limited, these findings provide a rational basis for future clinical trials. (4) ATRA-based combination therapies represent a promising strategy to extend differentiation therapy beyond APL. This review, authored solely by the investigator, highlights molecular targets and potential enhancers warranting further clinical evaluation in AML.<\/jats:p>","DOI":"10.3390\/curroncol33010025","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T09:56:23Z","timestamp":1767347783000},"page":"25","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Reawakening Differentiation Therapy in Acute Myeloid Leukemia: A Comprehensive Review of ATRA-Based Combination Strategies"],"prefix":"10.3390","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0011-6065","authenticated-orcid":false,"given":"Shinichiro","family":"Takahashi","sequence":"first","affiliation":[{"name":"Division of Laboratory Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 1-15-1 Fukumuro, Miyagino-ku, Sendai 983-8536, Japan"},{"name":"Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1159\/000510980","article-title":"Current Understandings of Myeloid Differentiation Inducers in Leukemia Therapy","volume":"144","author":"Takahashi","year":"2021","journal-title":"Acta Haematol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1159\/000519769","article-title":"Kinase Inhibitors and Interferons as Other Myeloid Differentiation Inducers in Leukemia Therapy","volume":"145","author":"Takahashi","year":"2022","journal-title":"Acta Haematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"115709","DOI":"10.1016\/j.bcp.2023.115709","article-title":"Advances in acute myeloid leukemia differentiation therapy: A critical review","volume":"215","year":"2023","journal-title":"Biochem. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.ccell.2022.07.002","article-title":"Integrative analysis of drug response and clinical outcome in acute myeloid leukemia","volume":"40","author":"Bottomly","year":"2022","journal-title":"Cancer Cell."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1186\/s13045-022-01368-3","article-title":"Oral arsenic and retinoic acid for high-risk acute promyelocytic leukemia","volume":"15","author":"Ma","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1111\/bjh.17752","article-title":"PML-RARA transcript levels at the end of induction therapy are associated with prognosis in non-high-risk acute promyelocytic leukaemia with all-trans retinoic acid plus arsenic in front-line therapy: Long-term follow-up of a single-centre cohort study","volume":"195","author":"Tang","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/S1470-2045(18)30295-X","article-title":"Oral arsenic plus retinoic acid versus intravenous arsenic plus retinoic acid for non-high-risk acute promyelocytic leukaemia: A non-inferiority, randomised phase 3 trial","volume":"19","author":"Zhu","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8903","DOI":"10.1158\/0008-5472.CAN-05-2726","article-title":"Sequential valproic acid\/all-trans retinoic acid treatment reprograms differentiation in refractory and high-risk acute myeloid leukemia","volume":"66","author":"Cimino","year":"2006","journal-title":"Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1002\/cncr.21589","article-title":"Clinical trial of valproic acid and all-trans retinoic acid in patients with poor-risk acute myeloid leukemia","volume":"104","author":"Bug","year":"2005","journal-title":"Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s00277-005-0026-8","article-title":"Results of a phase 2 study of valproic acid alone or in combination with all-trans retinoic acid in 75 patients with myelodysplastic syndrome and relapsed or refractory acute myeloid leukemia","volume":"84","author":"Kuendgen","year":"2005","journal-title":"Ann. Hematol."},{"key":"ref_11","first-page":"986","article-title":"Valproic acid and all-trans retinoic acid for the treatment of elderly patients with acute myeloid leukemia","volume":"90","author":"Raffoux","year":"2005","journal-title":"Haematologica"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e4","DOI":"10.3324\/haematol.2014.115055","article-title":"Biomodulatory therapy induces complete molecular remission in chemorefractory acute myeloid leukemia","volume":"100","author":"Thomas","year":"2015","journal-title":"Haematologica"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1200\/JCO.19.01053","article-title":"Valproate and Retinoic Acid in Combination With Decitabine in Elderly Nonfit Patients With Acute Myeloid Leukemia: Results of a Multicenter, Randomized, 2 \u00d7 2, Phase II Trial","volume":"38","author":"Grishina","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"34","DOI":"10.18632\/oncotarget.106","article-title":"Phase 2 clinical trial of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome","volume":"1","author":"Raffoux","year":"2010","journal-title":"Oncotarget"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/s41375-020-0892-z","article-title":"A proof of concept phase I\/II pilot trial of LSD1 inhibition by tranylcypromine combined with ATRA in refractory\/relapsed AML patients not eligible for intensive therapy","volume":"35","author":"Wass","year":"2021","journal-title":"Leukemia"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s13045-019-0811-9","article-title":"LSD1\/KDM1A inhibitors in clinical trials: Advances and prospects","volume":"12","author":"Fang","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1158\/1078-0432.CCR-20-4054","article-title":"Clinical Responsiveness to All-trans Retinoic Acid Is Potentiated by LSD1 Inhibition and Associated with a Quiescent Transcriptome in Myeloid Malignancies","volume":"27","author":"Tayari","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1080\/10428194.2018.1443330","article-title":"A phase-1 study of dasatinib plus all-trans retinoic acid in acute myeloid leukemia","volume":"59","author":"Redner","year":"2018","journal-title":"Leuk. Lymphoma"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Klobuch, S., Steinberg, T., Bruni, E., Mirbeth, C., Heilmeier, B., Ghibelli, L., Herr, W., Reichle, A., and Thomas, S. (2018). Biomodulatory Treatment With Azacitidine, All-trans Retinoic Acid and Pioglitazone Induces Differentiation of Primary AML Blasts Into Neutrophil Like Cells Capable of ROS Production and Phagocytosis. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.01380"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1158\/1535-7163.MCT-23-0528","article-title":"The CDK4\/6 Inhibitor Palbociclib Synergizes with ATRA to Induce Differentiation in AML","volume":"23","author":"Hu","year":"2024","journal-title":"Mol. Cancer Ther."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Novikova, S., Tolstova, T., Kurbatov, L., Farafonova, T., Tikhonova, O., Soloveva, N., Rusanov, A., and Zgoda, V. (2024). Systems Biology for Drug Target Discovery in Acute Myeloid Leukemia. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25094618"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1111\/j.1432-1033.1997.t01-2-00527.x","article-title":"Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5","volume":"243","author":"Meijer","year":"1997","journal-title":"Eur. J. Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.18632\/oncotarget.27508","article-title":"Roscovitine enhances all-trans retinoic acid (ATRA)-induced nuclear enrichment of an ensemble of activated signaling molecules and augments ATRA-induced myeloid cell differentiation","volume":"11","author":"Rashid","year":"2020","journal-title":"Oncotarget"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"109555","DOI":"10.1016\/j.cellsig.2020.109555","article-title":"Roscovitine enhances All-trans retinoic acid (ATRA)-induced leukemia cell differentiation: Novel effects on signaling molecules for a putative Cdk2 inhibitor","volume":"71","author":"Rashid","year":"2020","journal-title":"Cell Signal."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"104545","DOI":"10.1016\/j.phrs.2019.104545","article-title":"CDK2 suppression synergizes with all-trans-retinoic acid to overcome the myeloid differentiation blockade of AML cells","volume":"151","author":"Shao","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1158\/1078-0432.CCR-15-0663","article-title":"Sorafenib Inhibition of Mcl-1 Accelerates ATRA-Induced Apoptosis in Differentiation-Responsive AML Cells","volume":"22","author":"Wang","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.1158\/1535-7163.MCT-07-0514","article-title":"Inhibition of Src family kinases enhances retinoic acid induced gene expression and myeloid differentiation","volume":"6","author":"Miranda","year":"2007","journal-title":"Mol. Cancer Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.fct.2017.10.053","article-title":"Dasatinib synergizes with ATRA to trigger granulocytic differentiation in ATRA resistant acute promyelocytic leukemia cell lines via Lyn inhibition-mediated activation of RAF-1\/MEK\/ERK","volume":"119","author":"Ding","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s12935-016-0314-5","article-title":"Lyn, a tyrosine kinase closely linked to the differentiation status of primary acute myeloid leukemia blasts, associates with negative regulation of all-trans retinoic acid (ATRA) and dihydroxyvitamin D3 (VD3)-induced HL-60 cells differentiation","volume":"16","author":"Iriyama","year":"2016","journal-title":"Cancer Cell Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1038\/leu.2011.390","article-title":"Src inhibitors, PP2 and dasatinib, increase retinoic acid-induced association of Lyn and c-Raf (S259) and enhance MAPK-dependent differentiation of myeloid leukemia cells","volume":"26","author":"Congleton","year":"2012","journal-title":"Leukemia"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/leu.2009.267","article-title":"Dasatinib promotes ATRA-induced differentiation of AML cells","volume":"24","author":"Kropf","year":"2010","journal-title":"Leukemia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"126","DOI":"10.4143\/crt.2013.45.2.126","article-title":"Src Family Kinase Inhibitor PP2 Has Different Effects on All-Trans-Retinoic Acid or Arsenic Trioxide-Induced Differentiation of an Acute Promyelocytic Leukemia Cell Line","volume":"45","author":"Yoon","year":"2013","journal-title":"Cancer Res. Treat."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Heo, S.K., Noh, E.K., Yoon, D.J., Jo, J.C., Choi, Y., Koh, S., Baek, J.H., Park, J.H., Min, Y.J., and Kim, H. (2015). Radotinib Induces Apoptosis of CD11b+ Cells Differentiated from Acute Myeloid Leukemia Cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0129853"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.bcp.2014.02.019","article-title":"Autophagy contributes to dasatinib-induced myeloid differentiation of human acute myeloid leukemia cells","volume":"89","author":"Xie","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_35","first-page":"906","article-title":"Combination of enzastaurin and ATRA exerts dose-dependent dual effects on ATRA-resistant acute promyelocytic leukemia cells","volume":"9","author":"Liang","year":"2019","journal-title":"Am. J. Cancer Res."},{"key":"ref_36","first-page":"7836","article-title":"Enzastaurin enhances ATRA-induced differentiation of acute myeloid leukemia cells","volume":"12","author":"Li","year":"2020","journal-title":"Am. J. Transl. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3072","DOI":"10.3892\/or.2016.5123","article-title":"Staurosporine enhances ATRA-induced granulocytic differentiation in human leukemia U937 cells via the MEK\/ERK signaling pathway","volume":"36","author":"Shi","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1007\/s12185-020-03026-1","article-title":"Salt-inducible kinase inhibition sensitizes human acute myeloid leukemia cells to all-trans retinoic acid-induced differentiation","volume":"113","author":"Zhang","year":"2021","journal-title":"Int. J. Hematol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Wang, K., Ou, Z., Deng, G., Li, S., Su, J., Xu, Y., Zhou, R., Hu, W., and Chen, F. (2022). The Translational Landscape Revealed the Sequential Treatment Containing ATRA plus PI3K\/AKT Inhibitors as an Efficient Strategy for AML. Ther. Pharm., 14.","DOI":"10.3390\/pharmaceutics14112329"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1002\/ijc.24472","article-title":"Inhibition of mammalian target of rapamycin signaling potentiates the effects of all-trans retinoic acid to induce growth arrest and differentiation of human acute myelogenous leukemia cells","volume":"125","author":"Nishioka","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"de Almeida, L.Y., Pereira-Martins, D.A., Weinh\u00e4user, I., Ortiz, C., C\u00e2ndido, L.A., Lange, A.P., De Abreu, N.F., Mendonza, S.E.S., Wagatsuma, V.M.d.D., and Nascimento, M.C.D. (2021). The Combination of Gefitinib With ATRA and ATO Induces Myeloid Differentiation in Acute Promyelocytic Leukemia Resistant Cells. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.686445"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2978","DOI":"10.4161\/cc.26016","article-title":"EGFR inhibitors exacerbate differentiation and cell cycle arrest induced by retinoic acid and vitamin D3 in acute myeloid leukemia cells","volume":"12","author":"Lainey","year":"2013","journal-title":"Cell Cycle"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.1080\/10428194.2021.1961231","article-title":"Trametinib enhances ATRA-induced differentiation in AML cells","volume":"62","author":"Lu","year":"2021","journal-title":"Leuk. Lymphoma"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1182\/blood-2015-05-646786","article-title":"All-trans retinoic acid synergizes with FLT3 inhibition to eliminate FLT3\/ITD+ leukemia stem cells in vitro and in vivo","volume":"127","author":"Ma","year":"2016","journal-title":"Blood"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s11523-021-00830-5","article-title":"Selective Inhibition of JAK1 Primes STAT5-Driven Human Leukemia Cells for ATRA-Induced Differentiation","volume":"16","author":"Ramsey","year":"2021","journal-title":"Target Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"24589","DOI":"10.1038\/srep24589","article-title":"The HER2 inhibitor TAK165 Sensitizes Human Acute Myeloid Leukemia Cells to Retinoic Acid-Induced Myeloid Differentiation by activating MEK\/ERK mediated RARalpha\/STAT1 axis","volume":"6","author":"Shao","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.lfs.2016.02.054","article-title":"Arsenic trioxide augments all-trans retinoic acid-induced differentiation of HL-60 cells","volume":"149","author":"Sumi","year":"2016","journal-title":"Life Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1158\/0008-5472.CAN-17-3361","article-title":"Targeting the SUMO Pathway Primes All-trans Retinoic Acid-Induced Differentiation of Nonpromyelocytic Acute Myeloid Leukemias","volume":"78","author":"Baik","year":"2018","journal-title":"Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.3109\/10428194.2010.501535","article-title":"Arsenic trioxide cooperates with all trans retinoic acid to enhance mitogen-activated protein kinase activation and differentiation in PML-RARalpha negative human myeloblastic leukemia cells","volume":"51","author":"Nayak","year":"2010","journal-title":"Leuk. Lymphoma"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"331","DOI":"10.3390\/hematolrep15020035","article-title":"Combination Therapies with Kinase Inhibitors for Acute Myeloid Leukemia Treatment","volume":"15","author":"Takahashi","year":"2023","journal-title":"Hematol. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.advenzreg.2007.11.002","article-title":"Src family kinases and the MEK\/ERK pathway in the regulation of myeloid differentiation and myeloid leukemogenesis","volume":"48","author":"Johnson","year":"2008","journal-title":"Adv. Enzyme Regul."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.critrevonc.2017.02.003","article-title":"Enzastaurin: A lesson in drug development","volume":"112","author":"Bourhill","year":"2017","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13045-016-0294-x","article-title":"Epidermal growth factor receptor is expressed and active in a subset of acute myeloid leukemia","volume":"9","author":"Mahmud","year":"2016","journal-title":"J. Hematol. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1756-8722-4-13","article-title":"Downstream molecular pathways of FLT3 in the pathogenesis of acute myeloid leukemia: Biology and therapeutic implications","volume":"4","author":"Takahashi","year":"2011","journal-title":"J. Hematol. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/s41392-023-01468-7","article-title":"Evolving cognition of the JAK-STAT signaling pathway: Autoimmune disorders and cancer","volume":"8","author":"Xue","year":"2023","journal-title":"Signal Transduct Target Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/ncb1717","article-title":"Arsenic degrades PML or PML-RARalpha through a SUMO-triggered RNF4\/ubiquitin-mediated pathway","volume":"10","author":"Jeanne","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1016\/j.celrep.2014.05.016","article-title":"The ROS\/SUMO axis contributes to the response of acute myeloid leukemia cells to chemotherapeutic drugs","volume":"7","author":"Bossis","year":"2014","journal-title":"Cell Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"865","DOI":"10.3892\/ijo.2013.2236","article-title":"Enhancement of differentiation induction and upregulation of CCAAT\/enhancer-binding proteins and PU.1 in NB4 cells treated with combination of ATRA and valproic acid","volume":"44","author":"Iriyama","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Benjamin, D.N., O\u2019dOnovan, T.R., Laursen, K.B., Orfali, N., Cahill, M.R., Mongan, N.P., Gudas, L.J., and McKenna, S.L. (2022). All-Trans-Retinoic Acid Combined With Valproic Acid Can Promote Differentiation in Myeloid Leukemia Cells by an Autophagy Dependent Mechanism. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.848517"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1038\/s41375-022-01530-3","article-title":"Co-targeting leukemia-initiating cells and leukemia bulk leads to disease eradication","volume":"36","author":"Moretti","year":"2022","journal-title":"Leukemia"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1038\/leu.2012.39","article-title":"Valproic acid induces differentiation and transient tumor regression, but spares leukemia-initiating activity in mouse models of APL","volume":"26","author":"Leiva","year":"2012","journal-title":"Leukemia"},{"key":"ref_62","first-page":"1027","article-title":"Growth inhibition of myeloid leukemia cells by troglitazone, a ligand for peroxisome proliferator activated receptor gamma, and retinoids","volume":"15","author":"Asou","year":"1999","journal-title":"Int. J. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Blagitko-Dorfs, N., Jiang, Y., Duque-Afonso, J., Hiller, J., Yalcin, A., Greve, G., Abdelkarim, M., Hackanson, B., and L\u00fcbbert, M. (2013). Epigenetic priming of AML blasts for all-trans retinoic acid-induced differentiation by the HDAC class-I selective inhibitor entinostat. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075258"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1038\/sj.leu.2401508","article-title":"Histone deacetylase inhibitors are the potent inducer\/enhancer of differentiation in acute myeloid leukemia: A new approach to anti-leukemia therapy","volume":"13","author":"Kosugi","year":"1999","journal-title":"Leukemia"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1038\/sj.leu.2401468","article-title":"Augmentation of phenylbutyrate-induced differentiation of myeloid leukemia cells using all-trans retinoic acid","volume":"13","author":"Yu","year":"1999","journal-title":"Leukemia"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S0140-6736(18)31041-9","article-title":"Acute myeloid leukaemia","volume":"392","author":"Short","year":"2018","journal-title":"Lancet"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1158\/2159-8290.CD-19-1011","article-title":"Advances in the Treatment of Acute Myeloid Leukemia: New Drugs and New Challenges","volume":"10","author":"Short","year":"2020","journal-title":"Cancer Discov."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1084\/jem.20150736","article-title":"Isocitrate dehydrogenase 1 mutations prime the all-trans retinoic acid myeloid differentiation pathway in acute myeloid leukemia","volume":"213","author":"Boutzen","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Sabatier, M., Boet, E., Zaghdoudi, S., Guiraud, N., Hucteau, A., Polley, N., Cognet, G., Saland, E., Lauture, L., and Farge, T. (2021). Activation of Vitamin D Receptor Pathway Enhances Differentiating Capacity in Acute Myeloid Leukemia with Isocitrate Dehydrogenase Mutations. Cancers, 13.","DOI":"10.20944\/preprints202108.0529.v1"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/nm.2661","article-title":"Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia","volume":"18","author":"Schenk","year":"2012","journal-title":"Nat. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1038\/s41375-018-0375-7","article-title":"LSD1 inhibition by tranylcypromine derivatives interferes with GFI1-mediated repression of PU.1 target genes and induces differentiation in AML","volume":"33","author":"Barth","year":"2019","journal-title":"Leukemia"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"8183","DOI":"10.1039\/C7TB01895A","article-title":"Impact of structurally modifying hyaluronic acid on CD44 interaction","volume":"5","author":"Bhattacharya","year":"2017","journal-title":"J. Mater. Chem. B"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/sj.leu.2404179","article-title":"A novel retinoic\/butyric hyaluronan ester for the treatment of acute promyelocytic leukemia: Preliminary preclinical results","volume":"20","author":"Coradini","year":"2006","journal-title":"Leukemia"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1289\/ehp.8140233","article-title":"The role of metals in carcinogenesis: Biochemistry and metabolism","volume":"40","author":"Jennette","year":"1981","journal-title":"Environ. Health Perspect."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1093\/carcin\/bgn179","article-title":"Selenite reactivates silenced genes by modifying DNA methylation and histones in prostate cancer cells","volume":"29","author":"Xiang","year":"2008","journal-title":"Carcinogenesis"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.canlet.2009.03.010","article-title":"Selenite is a potent cytotoxic agent for human primary AML cells","volume":"282","author":"Olm","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"74686","DOI":"10.18632\/oncotarget.12531","article-title":"Selenite promotes all-trans retinoic acid-induced maturation of acute promyelocytic leukemia cells","volume":"7","author":"Misra","year":"2016","journal-title":"Oncotarget"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.cell.2016.08.057","article-title":"Inhibition of Dihydroorotate Dehydrogenase Overcomes Differentiation Blockade in Acute Myeloid Leukemia","volume":"167","author":"Sykes","year":"2016","journal-title":"Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1038\/s41375-019-0461-5","article-title":"The novel dihydroorotate dehydrogenase (DHODH) inhibitor BAY 2402234 triggers differentiation and is effective in the treatment of myeloid malignancies","volume":"33","author":"Christian","year":"2019","journal-title":"Leukemia"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.3109\/10428194.2013.876633","article-title":"5-Aminoimidazole-4-carboxamide ribonucleoside induces differentiation of acute myeloid leukemia cells","volume":"55","author":"Lalic","year":"2014","journal-title":"Leuk. Lymphoma"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Dembitz, V., Lalic, H., Kodvanj, I., Tomic, B., Batinic, J., Dubravcic, K., Batinic, D., Bedalov, A., and Visnjic, D. (2020). 5-aminoimidazole-4-carboxamide ribonucleoside induces differentiation in a subset of primary acute myeloid leukemia blasts. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-07533-6"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Suzuki, S., Suzuki, S., Sato-Nagaoka, Y., Ito, C., and Takahashi, S. (2024). Identification of triciribine as a novel myeloid cell differentiation inducer. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0303428"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4369","DOI":"10.1158\/0008-5472.CAN-07-6559","article-title":"Identification of 6-benzylthioinosine as a myeloid leukemia differentiation-inducing compound","volume":"68","author":"Wald","year":"2008","journal-title":"Cancer Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"818","DOI":"10.2174\/1568009616666160617103301","article-title":"Pyrimethamine as a Potent and Selective Inhibitor of Acute Myeloid Leukemia Identified by High-throughput Drug Screening","volume":"16","author":"Sharma","year":"2016","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Xu, Z., Shao, J., Li, L., Peng, X., Chen, M., Li, G., Yan, H., Yang, B., Luo, P., and He, Q. (2016). All-trans retinoic acid synergizes with topotecan to suppress AML cells via promoting RARalpha-mediated DNA damage. BMC Cancer, 16.","DOI":"10.1186\/s12885-015-2010-6"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0006-2952(01)00848-6","article-title":"Matrix and serine protease expression during leukemic cell differentiation induced by aclacinomycin and all-trans-retinoic acid","volume":"63","author":"Devy","year":"2002","journal-title":"Biochem. Pharmacol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/S0301-472X(02)00905-0","article-title":"The catalytic DNA topoisomerase II inhibitor ICRF-193 and all-trans retinoic acid cooperatively induce granulocytic differentiation of acute promyelocytic leukemia cells: Candidate drugs for chemo-differentiation therapy against acute promyelocytic leukemia","volume":"30","author":"Niitsu","year":"2002","journal-title":"Exp. Hematol."},{"key":"ref_88","first-page":"178","article-title":"Induction of differentiation of acute promyelocytic leukemia cells by a cytidine deaminase-resistant analogue of 1-beta-D-arabinofuranosylcytosine, 1-(2-deoxy-2-methylene-beta-D-erythro-pentofuranosyl)cytidine","volume":"61","author":"Niitsu","year":"2001","journal-title":"Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1159\/000039753","article-title":"In vitro apoptotic response of freshly isolated chronic myeloid leukemia cells to all-trans retinoic acid and cytosine arabinoside","volume":"104","author":"Stagno","year":"2000","journal-title":"Acta Haematol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0145-2126(99)00143-5","article-title":"Myeloid and monocytoid leukemia cells have different sensitivity to differentiation-inducing activity of deoxyadenosine analogs","volume":"24","author":"Niitsu","year":"2000","journal-title":"Leuk Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1006\/bbrc.1997.7250","article-title":"Induction of differentiation of human myeloid leukemia cells by 2\u2032-deoxycoformycin in combination with 2\u2032-deoxyadenosine","volume":"238","author":"Niitsu","year":"1997","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"261","DOI":"10.3109\/10428199909050951","article-title":"Adenosine analogs as possible differentiation-inducing agents against acute myeloid leukemia","volume":"34","author":"Niitsu","year":"1999","journal-title":"Leuk. Lymphoma"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.canlet.2019.11.013","article-title":"Dysregulation of de novo nucleotide biosynthetic pathway enzymes in cancer and targeting opportunities","volume":"470","author":"Robinson","year":"2020","journal-title":"Cancer Lett."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"15257","DOI":"10.1074\/jbc.RA119.009396","article-title":"The ribonucleoside AICAr induces differentiation of myeloid leukemia by activating the ATR\/Chk1 via pyrimidine depletion","volume":"294","author":"Dembitz","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"15458","DOI":"10.1038\/s41598-018-33453-4","article-title":"Characterization of a novel AICARFT inhibitor which potently elevates ZMP and has anti-tumor activity in murine models","volume":"8","author":"Brooks","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1016\/j.celrep.2017.10.029","article-title":"The mTORC1 Signaling Network Senses Changes in Cellular Purine Nucleotide Levels","volume":"21","author":"Hoxhaj","year":"2017","journal-title":"Cell Rep."},{"key":"ref_97","first-page":"494","article-title":"Signaling effect, combinations, and clinical applications of triciribine","volume":"87","author":"Takahashi","year":"2024","journal-title":"J. Chemother."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4045","DOI":"10.1016\/0006-2952(89)90685-0","article-title":"Inhibition of two enzymes in de novo purine nucleotide synthesis by triciribine phosphate (TCN-P)","volume":"38","author":"Moore","year":"1989","journal-title":"Biochem. Pharmacol."},{"key":"ref_99","first-page":"2867","article-title":"Inhibition of purine nucleotide metabolism by 6-methylthiopurine ribonucleoside and structurally related compounds","volume":"33","author":"Shantz","year":"1973","journal-title":"Cancer Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0083-6729(08)00409-3","article-title":"Regulation of human dihydrofolate reductase activity and expression","volume":"79","author":"Abali","year":"2008","journal-title":"Vitam Horm"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/0305-7372(94)90011-6","article-title":"Topoisomerase I inhibitors: Topotecan and irenotecan","volume":"20","author":"Creemers","year":"1994","journal-title":"Cancer Treat Rev."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1182\/blood.2022018739","article-title":"MDM2 and BCL-2: To p53 or not to p53?","volume":"141","author":"Wang","year":"2023","journal-title":"Blood"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/nature03579","article-title":"An inhibitor of Bcl-2 family proteins induces regression of solid tumours","volume":"435","author":"Oltersdorf","year":"2005","journal-title":"Nature"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1080\/10428194.2020.1839648","article-title":"Differentiation of acute myeloid leukemia (AML) cells with ATRA reduces (18)F-FDG uptake and increases sensitivity towards ABT-737-induced apoptosis","volume":"62","author":"Buschner","year":"2021","journal-title":"Leuk. Lymphoma"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.yexcr.2014.07.024","article-title":"BCL-xL\/MCL-1 inhibition and RARgamma antagonism work cooperatively in human HL60 leukemia cells","volume":"327","author":"Perri","year":"2014","journal-title":"Exp. Cell Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s10637-010-9512-5","article-title":"Nutlin-1 strengthened anti-proliferation and differentiation-inducing activity of ATRA in ATRA-treated p-glycoprotein deregulated human myelocytic leukemia cells","volume":"30","author":"Zhang","year":"2012","journal-title":"Investig. New Drugs"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12935-015-0176-2","article-title":"Granulocyte colony-stimulating factor potentiates all-trans retinoic acid-induced granulocytic differentiation in acute promyelocytic leukemia cell line HT93A","volume":"15","author":"Uchino","year":"2015","journal-title":"Cancer Cell Int."},{"key":"ref_108","first-page":"1301","article-title":"Potentiated maturation with a high proliferating activity of acute promyelocytic leukemia induced in vitro by granulocyte or granulocyte\/macrophage colony-stimulating factors in combination with all-trans retinoic acid","volume":"8","author":"Imaizumi","year":"1994","journal-title":"Leukemia"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1007\/BF02983213","article-title":"Granulocyte colony-stimulating factor-induced terminal maturation of human myeloid cells is specifically associated with up-regulation of receptor-mediated function and CD10 expression","volume":"77","author":"Inazawa","year":"2003","journal-title":"Int. J. Hematol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S0145-2126(97)00179-3","article-title":"GCSF augments post-progenitor proliferation in serum-free cultures of myelodysplastic marrow while ATRA enhances maturation","volume":"22","author":"Truran","year":"1998","journal-title":"Leuk. Res."},{"key":"ref_111","first-page":"1951","article-title":"Retinoic acid combined with GM-CSF induces morphological changes with segmented nuclei in human myeloblastic leukemia ML-1 cells","volume":"17","author":"Oka","year":"1997","journal-title":"Anticancer Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.2169\/internalmedicine.34.1186","article-title":"Combination therapy with granulocyte colony-stimulating factor, all-trans retinoic acid, and low-dose cytotoxic drugs for acute myelogenous leukemia","volume":"34","author":"Usuki","year":"1995","journal-title":"Intern. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"648","DOI":"10.2169\/internalmedicine.32.648","article-title":"The combined effects of all-trans retinoic acid and granulocyte colony-stimulating factor as a differentiation induction therapy for acute promyelocytic leukemia","volume":"32","author":"Tsurumi","year":"1993","journal-title":"Intern. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"33280","DOI":"10.1074\/jbc.M002840200","article-title":"Dimerization with retinoid X receptors and phosphorylation modulate the retinoic acid-induced degradation of retinoic acid receptors alpha and gamma through the ubiquitin-proteasome pathway","volume":"275","author":"Kopf","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1158\/1535-7163.MCT-12-0433","article-title":"Bortezomib sensitizes human acute myeloid leukemia cells to all-trans-retinoic acid-induced differentiation by modifying the RARalpha\/STAT1 axis","volume":"12","author":"Ying","year":"2013","journal-title":"Mol. Cancer Ther."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1002\/mc.20687","article-title":"Inhibition of all-trans-retinoic acid-induced proteasome activation potentiates the differentiating effect of retinoid in acute myeloid leukemia cells","volume":"50","author":"Fang","year":"2011","journal-title":"Mol. Carcinog."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1182\/blood-2004-03-1074","article-title":"Retinoids and myelomonocytic growth factors cooperatively activate RARA and induce human myeloid leukemia cell differentiation via MAP kinase pathways","volume":"105","author":"Glasow","year":"2005","journal-title":"Blood"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"S25","DOI":"10.1016\/0090-1229(92)90038-P","article-title":"Recombinant human hematopoietic growth factors in the treatment of cytopenias","volume":"62","author":"Grosh","year":"1992","journal-title":"Clin. Immunol. Immunopathol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1515\/oncologie-2025-0155","article-title":"A mini-review: The role of glycosylation in acute myeloid leukemia and its potential for treatment","volume":"27","author":"Takahashi","year":"2025","journal-title":"Oncologie"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"149541","DOI":"10.1016\/j.bbrc.2024.149541","article-title":"Fucosylation inhibitor 6-alkynylfucose enhances the ATRA-induced differentiation effect on acute promyelocytic leukemia cells","volume":"710","author":"Suzuki","year":"2024","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"102678","DOI":"10.1016\/j.ebiom.2020.102678","article-title":"Epigenetic activation of O-linked beta-N-acetylglucosamine transferase overrides the differentiation blockage in acute leukemia","volume":"54","author":"Haverkamp","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1083\/jcb.201501101","article-title":"A little sugar goes a long way: The cell biology of O-GlcNAc","volume":"208","author":"Bond","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/s10020-022-00544-y","article-title":"O-GlcNAcylation: An important post-translational modification and a potential therapeutic target for cancer therapy","volume":"28","author":"Lu","year":"2022","journal-title":"Mol. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nrc3114","article-title":"O-GlcNAc signalling: Implications for cancer cell biology","volume":"11","author":"Slawson","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1074\/jbc.RA118.005993","article-title":"O-GlcNAc homeostasis contributes to cell fate decisions during hematopoiesis","volume":"294","author":"Zhang","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"4524","DOI":"10.1158\/0008-5472.CAN-06-3686","article-title":"Suppressive effects of statins on acute promyelocytic leukemia cells","volume":"67","author":"Sassano","year":"2007","journal-title":"Cancer Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"3069","DOI":"10.1182\/blood-2012-01-403493","article-title":"Fluvastatin inhibits FLT3 glycosylation in human and murine cells and prolongs survival of mice with FLT3\/ITD leukemia","volume":"120","author":"Williams","year":"2012","journal-title":"Blood"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"9103","DOI":"10.1038\/s41598-021-88478-z","article-title":"(-)-Epigallocatechin-3-gallate induces apoptosis and differentiation in leukaemia by targeting reactive oxygen species and PIN1","volume":"11","author":"Shiraishi","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1365-2141.2009.08040.x","article-title":"Epigallocatechin-3-gallate induces cell death in acute myeloid leukaemia cells and supports all-trans retinoic acid-induced neutrophil differentiation via death-associated protein kinase 2","volume":"149","author":"Britschgi","year":"2010","journal-title":"Br. J. Haematol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"899","DOI":"10.3892\/ijo.2017.4086","article-title":"Epigallocatechin-3-gallate promotes all-trans retinoic acid-induced maturation of acute promyelocytic leukemia cells via PTEN","volume":"51","author":"Yao","year":"2017","journal-title":"Int. J. Oncol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1016\/j.bbrc.2017.12.030","article-title":"Dihydromyricetin sensitizes human acute myeloid leukemia cells to retinoic acid-induced myeloid differentiation by activating STAT1","volume":"495","author":"He","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/j.1527-3458.2005.tb00266.x","article-title":"Therapeutic potential of wogonin: A naturally occurring flavonoid","volume":"11","author":"Tai","year":"2005","journal-title":"CNS Drug Rev."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1182\/blood-2007-06-096198","article-title":"Wogonin preferentially kills malignant lymphocytes and suppresses T-cell tumor growth by inducing PLCgamma1- and Ca2+-dependent apoptosis","volume":"111","author":"Baumann","year":"2008","journal-title":"Blood"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"3682","DOI":"10.1182\/blood-2012-11-466219","article-title":"Wogonoside induces cell cycle arrest and differentiation by affecting expression and subcellular localization of PLSCR1 in AML cells","volume":"121","author":"Chen","year":"2013","journal-title":"Blood"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"e2768","DOI":"10.1038\/cddis.2017.175","article-title":"PLSCR1\/IP3R1\/Ca2+ axis contributes to differentiation of primary AML cells induced by wogonoside","volume":"8","author":"Li","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Qu, M., Duan, Y., Zhao, M., Wang, Z., Zhao, M., Zhao, Y., Wang, H., Ke, Y., Liu, Y., and Liu, H.M. (2021). Jiyuan Oridonin A Overcomes Differentiation Blockade in Acute Myeloid Leukemia Cells With MLL Rearrangements via Multiple Signaling Pathways. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.659720"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.7150\/jca.83219","article-title":"Differentiation of imatinib-resistant chronic myeloid leukemia cells with BCR-ABL-T315I mutation induced by Jiyuan Oridonin A","volume":"14","author":"Xu","year":"2023","journal-title":"J. Cancer"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.omto.2020.06.008","article-title":"A Small Molecule Inhibitor, OGP46, Is Effective against Imatinib-Resistant BCR-ABL Mutations via the BCR-ABL\/JAK-STAT Pathway","volume":"18","author":"Wei","year":"2020","journal-title":"Mol. Ther.-Oncolytics"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Zhao, M., Wang, J., Qu, M., Zhao, Y., Wang, H., Ke, Y., Liu, Y., Lei, Z.N., Liu, H.M., and Hu, Z. (2021). OGP46 Induces Differentiation of Acute Myeloid Leukemia Cells via Different Optimal Signaling Pathways. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.652972"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"107127","DOI":"10.1016\/j.toxicon.2023.107127","article-title":"Silymarin in combination with ATRA enhances apoptosis induction in human acute promyelocytic NB4 cells","volume":"228","author":"Parsa","year":"2023","journal-title":"Toxicon"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"5289","DOI":"10.1182\/blood-2010-02-267963","article-title":"Pharicin B stabilizes retinoic acid receptor-alpha and presents synergistic differentiation induction with ATRA in myeloid leukemic cells","volume":"116","author":"Gu","year":"2010","journal-title":"Blood"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1248\/cpb.41.926","article-title":"Analgesic component of Notopterygium incisum Ting","volume":"41","author":"Okuyama","year":"1993","journal-title":"Chem. Pharm. Bull"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.2147\/DDDT.S189969","article-title":"Notopterol-induced apoptosis and differentiation in human acute myeloid leukemia HL-60 cells","volume":"13","author":"Huang","year":"2019","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"851","DOI":"10.3390\/md12020851","article-title":"Fucoidan as a marine anticancer agent in preclinical development","volume":"12","author":"Kwak","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"46028","DOI":"10.18632\/oncotarget.10016","article-title":"Fucoidan enhances the therapeutic potential of arsenic trioxide and all-trans retinoic acid in acute promyelocytic leukemia, in vitro and in vivo","volume":"7","author":"Atashrazm","year":"2016","journal-title":"Oncotarget"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1046\/j.1365-2141.2001.02601.x","article-title":"Induction of the monocytic differentiation of myeloid leukaemia cells by cotylenin A, a plant growth regulator","volume":"112","author":"Yamada","year":"2001","journal-title":"Br. J. Haematol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1046\/j.1365-2141.2001.03029.x","article-title":"Differentiation of human acute myeloid leukaemia cells in primary culture in response to cotylenin A, a plant growth regulator","volume":"114","author":"Yamada","year":"2001","journal-title":"Br. J. Haematol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/227379a0","article-title":"Isolation of a new plant growth substance with cytokinin-like activity","volume":"227","author":"Sassa","year":"1970","journal-title":"Nature"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1080\/1042819021000006493","article-title":"Differentiation of human myeloid leukemia cells by plant redifferentiation-inducing hormones","volume":"43","author":"Honma","year":"2002","journal-title":"Leuk. Lymphoma"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1080\/10428190290026222","article-title":"Cotylenin A--a plant growth regulator as a differentiation-inducing agent against myeloid leukemia","volume":"43","author":"Honma","year":"2002","journal-title":"Leuk. Lymphoma"},{"key":"ref_151","first-page":"343","article-title":"Tyrosine kinase inhibitor emodin suppresses growth of HER-2\/neu-overexpressing breast cancer cells in athymic mice and sensitizes these cells to the inhibitory effect of paclitaxel","volume":"5","author":"Zhang","year":"1999","journal-title":"Clin Cancer Res."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1182\/blood-2006-04-015537","article-title":"Emodin and DHA potently increase arsenic trioxide interferon-alpha-induced cell death of HTLV-I-transformed cells by generation of reactive oxygen species and inhibition of Akt and AP-1","volume":"109","author":"Brown","year":"2007","journal-title":"Blood"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.3892\/ijo.2014.2610","article-title":"Emodin enhances ATRA-induced differentiation and induces apoptosis in acute myeloid leukemia cells","volume":"45","author":"Chen","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1007\/s12185-010-0627-4","article-title":"Ellagic acid, a natural polyphenolic compound, induces apoptosis and potentiates retinoic acid-induced differentiation of human leukemia HL-60 cells","volume":"92","author":"Hagiwara","year":"2010","journal-title":"Int. J. Hematol."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Gupta, K., Chakrabarti, A., Rana, S., Ramdeo, R., Roth, B.L., Agarwal, M.L., Tse, W., Agarwal, M.K., and Wald, D.N. (2011). Securinine, a myeloid differentiation agent with therapeutic potential for AML. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021203"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"19185","DOI":"10.1039\/D1RA02558A","article-title":"Unique indolizidine alkaloid securinine is a promising scaffold for the development of neuroprotective and antitumor drugs","volume":"11","author":"Klochkov","year":"2021","journal-title":"RSC Adv."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/sj.leu.2402419","article-title":"Plant stress hormones suppress the proliferation and induce apoptosis in human cancer cells","volume":"16","author":"Fingrut","year":"2002","journal-title":"Leukemia"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1038\/sj.leu.2403421","article-title":"Induction of differentiation of human myeloid leukemia cells by jasmonates, plant hormones","volume":"18","author":"Ishii","year":"2004","journal-title":"Leukemia"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/leu.2008.347","article-title":"Gene expression profiles in differentiating leukemia cells induced by methyl jasmonate are similar to those of cytokinins and methyl jasmonate analogs induce the differentiation of human leukemia cells in primary culture","volume":"23","author":"Tsumura","year":"2009","journal-title":"Leukemia"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.canlet.2008.03.052","article-title":"Multi-targeted therapy of cancer by genistein","volume":"269","author":"Banerjee","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_161","first-page":"2618","article-title":"Induction of differentiation and DNA strand breakage in human HL-60 and K-562 leukemia cells by genistein","volume":"50","author":"Constantinou","year":"1990","journal-title":"Cancer Res."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.bcp.2008.10.035","article-title":"Regulation of genistein-induced differentiation in human acute myeloid leukaemia cells (HL60, NB4) Protein kinase modulation and reactive oxygen species generation","volume":"77","author":"Sanchez","year":"2009","journal-title":"Biochem. Pharmacol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1007\/BF02982118","article-title":"Resveratrol, a natural product derived from grapes, is a new inducer of differentiation in human myeloid leukemias","volume":"75","author":"Asou","year":"2002","journal-title":"Int. J. Hematol."},{"key":"ref_164","first-page":"305","article-title":"Differentiation of HL-60 myeloid leukemia cells induced by all-trans retinoic acid is enhanced in combination with caffeic acid","volume":"14","author":"Veselska","year":"2004","journal-title":"Int. J. Mol. Med."},{"key":"ref_165","first-page":"729","article-title":"Chinese herbal mixture PC SPES in treatment of prostate cancer (review)","volume":"17","author":"Darzynkiewicz","year":"2000","journal-title":"Int. J. Oncol."},{"key":"ref_166","first-page":"1203","article-title":"PC-SPES decreases proliferation and induces differentiation and apoptosis of human acute myeloid leukemia cells","volume":"23","author":"Ikezoe","year":"2003","journal-title":"Int. J. Oncol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"2698","DOI":"10.1158\/0008-5472.CAN-15-1616","article-title":"Natural Product Vibsanin A Induces Differentiation of Myeloid Leukemia Cells through PKC Activation","volume":"76","author":"Yu","year":"2016","journal-title":"Cancer Res."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1007\/s12272-001-2115-0","article-title":"Production, isolation and biological activity of nargenicin from Nocardia sp. CS682","volume":"31","author":"Sohng","year":"2008","journal-title":"Arch Pharm. Res."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.bbrc.2009.04.014","article-title":"Deamino-hydroxy-phoslactomycin B, a biosynthetic precursor of phoslactomycin, induces myeloid differentiation in HL-60 cells","volume":"383","author":"Simizu","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"950658","DOI":"10.1155\/2012\/950658","article-title":"Salinomycin as a drug for targeting human cancer stem cells","volume":"2012","author":"Naujokat","year":"2012","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1016\/j.bcp.2009.03.004","article-title":"Nargenicin enhances 1,25-dihydroxyvitamin D(3)- and all-trans retinoic acid-induced leukemia cell differentiation via PKCbetaI\/MAPK pathways","volume":"77","author":"Kim","year":"2009","journal-title":"Biochem. Pharmacol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.2174\/1871520623666230110121629","article-title":"Combined Application of Salinomycin and ATRA Induces Apoptosis and Differentiation of Acute Myeloid Leukemia Cells by Inhibiting WNT\/beta-Catenin Pathway","volume":"23","author":"Xi","year":"2023","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Pan, X.N., Chen, J.J., Wang, L.X., Xiao, R.Z., Liu, L.L., Fang, Z.G., Liu, Q., Long, Z.J., and Lin, D.J. (2014). Inhibition of c-Myc overcomes cytotoxic drug resistance in acute myeloid leukemia cells by promoting differentiation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0105381"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1038\/leu.2016.50","article-title":"LG-362B targets PML-RARalpha and blocks ATRA resistance of acute promyelocytic leukemia","volume":"30","author":"Wang","year":"2016","journal-title":"Leukemia"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1046\/j.1525-1500.1999.99052.x","article-title":"Furanonaphthoquinone analogs possessing preferential antitumor activity compared to normal cells","volume":"23","author":"Hirai","year":"1999","journal-title":"Cancer Detect. Prev."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1111\/j.1365-2141.2005.05803.x","article-title":"The synthetic furanonaphthoquinone induces growth arrest, apoptosis and differentiation in a variety of leukaemias and multiple myeloma cells","volume":"131","author":"Desmond","year":"2005","journal-title":"Br. J. Haematol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"7847","DOI":"10.1158\/0008-5472.CAN-05-1053","article-title":"Benzodithiophenes induce differentiation and apoptosis in human leukemia cells","volume":"65","author":"Jing","year":"2005","journal-title":"Cancer Res."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"3719","DOI":"10.1182\/blood-2002-03-0720","article-title":"Bis-indols: A novel class of molecules enhancing the cytodifferentiating properties of retinoids in myeloid leukemia cells","volume":"100","author":"Pisano","year":"2002","journal-title":"Blood"},{"key":"ref_179","first-page":"336","article-title":"A novel synthetic oleanane triterpenoid, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, with potent differentiating, antiproliferative, and anti-inflammatory activity","volume":"59","author":"Suh","year":"1999","journal-title":"Cancer Res."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1182\/blood.V99.1.326","article-title":"Novel triterpenoid CDDO-Me is a potent inducer of apoptosis and differentiation in acute myelogenous leukemia","volume":"99","author":"Konopleva","year":"2002","journal-title":"Blood"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/S0301-472X(00)00647-0","article-title":"Induction of differentiation of human myeloid leukemia cells by novel synthetic neurotrophic pyrimidine derivatives","volume":"29","author":"Honma","year":"2001","journal-title":"Exp. Hematol."},{"key":"ref_182","first-page":"198","article-title":"A novel uracil analog, 6-chloro-5-(2-propenyl)uracil, preferentially enhances growth inhibition and differentiation of myeloid leukemia cells induced by 1alpha,25-dihydroxyvitamin D3","volume":"26","author":"Kanatani","year":"1998","journal-title":"Exp. Hematol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1271\/bbb.67.1132","article-title":"Induction of differentiation in human promyelocytic leukemia HL-60 cell line by niacin-related compounds","volume":"67","author":"Iwata","year":"2003","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/S0021-9258(17)45263-X","article-title":"The Fate of Nicotinamide in the Mouse. Urinary Metabolites","volume":"240","author":"Chaykin","year":"1965","journal-title":"J. Biol. Chem."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1080\/00039896.1970.10665602","article-title":"Biological effect of oral administration of isonicotinic acid in mice","volume":"20","author":"Toth","year":"1970","journal-title":"Arch. Environ. Health"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"16792","DOI":"10.1038\/s41598-024-67670-x","article-title":"Drug exposure and risk factors of maculopathy in tamoxifen users","volume":"14","author":"Kwon","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.3892\/ijo.2016.3348","article-title":"Tamoxifen enhances the differentiation-inducing and growth-inhibitory effects of all-trans retinoic acid in acute promyelocytic leukemia cells","volume":"48","author":"Adachi","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1080\/15384101.2015.1033591","article-title":"Monocyte-macrophage differentiation of acute myeloid leukemia cell lines by small molecules identified through interrogation of the Connectivity Map database","volume":"14","author":"Manzotti","year":"2015","journal-title":"Cell Cycle"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.bbrc.2012.05.001","article-title":"Metformin induces differentiation in acute promyelocytic leukemia by activating the MEK\/ERK signaling pathway","volume":"422","author":"Huai","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1056\/NEJM197801262980402","article-title":"Effect of lithium on neutrophil mass and production","volume":"298","author":"Rothstein","year":"1978","journal-title":"N. Engl. J. Med."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/j.leukres.2004.03.017","article-title":"Analysis of the relationship between Scl transcription factor complex protein expression patterns and the effects of LiCl on ATRA-induced differentiation in blast cells from patients with acute myeloid leukemia","volume":"28","author":"Rice","year":"2004","journal-title":"Leuk. Res."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1182\/blood.V96.6.2262","article-title":"Maintenance of retinoic acid receptor alpha pools by granulocyte colony-stimulating factor and lithium chloride in all-trans retinoic acid-treated WEHI-3B leukemia cells: Relevance to the synergistic induction of terminal differentiation","volume":"96","author":"Finch","year":"2000","journal-title":"Blood"},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Villegas-V\u00e1zquez, E.Y., Quintas-Granados, L.I., Cort\u00e9s, H., Carmen, M.G.-D., Leyva-G\u00f3mez, G., Rodr\u00edguez-Morales, M., Bustamante-Montes, L.P., Silva-Adaya, D., P\u00e9rez-Plasencia, C., and Jacobo-Herrera, N. (2023). Lithium: A Promising Anticancer Agent. Life, 13.","DOI":"10.3390\/life13020537"},{"key":"ref_194","doi-asserted-by":"crossref","unstructured":"Ueda, M., Stefan, T., Stetson, L., Ignatz-Hoover, J.J., Tomlinson, B., Creger, R.J., Cooper, B., Lazarus, H.M., de Lima, M., and Wald, D.N. (2020). Phase I Trial of Lithium and Tretinoin for Treatment of Relapsed and Refractory Non-promyelocytic Acute Myeloid Leukemia. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.00327"},{"key":"ref_195","first-page":"806","article-title":"All-trans retinoic acid and 1 alpha,25-dihydroxyvitamin D3 co-operate to promote differentiation of the human promyeloid leukemia cell line HL60 to monocytes","volume":"8","author":"Brown","year":"1994","journal-title":"Leukemia"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exphem.2017.01.007","article-title":"Application of vitamin D and vitamin D analogs in acute myelogenous leukemia","volume":"50","author":"Cao","year":"2017","journal-title":"Exp. Hematol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.trecan.2020.04.002","article-title":"Targeting Glycosylation: A New Road for Cancer Drug Discovery","volume":"6","author":"Costa","year":"2020","journal-title":"Trends Cancer"},{"key":"ref_198","doi-asserted-by":"crossref","unstructured":"Wei, X., Wang, W., Yin, Q., Li, H., Ahmed, A., Ullah, R., Li, W., and Jing, L. (2024). In Vivo Chemical Screening in Zebrafish Embryos Identified FDA-Approved Drugs That Induce Differentiation of Acute Myeloid Leukemia Cells. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25147798"},{"key":"ref_199","first-page":"991","article-title":"Biological activity of all-trans-retinoic acid with and without tamoxifen and alpha-interferon 2a in breast cancer patients","volume":"17","author":"Toma","year":"2000","journal-title":"Int. J. Oncol."},{"key":"ref_200","first-page":"635","article-title":"Phase I\/II trial of all-trans retinoic acid and tamoxifen in patients with advanced breast cancer","volume":"4","author":"Budd","year":"1998","journal-title":"Clin. Cancer Res."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.1200\/JCO.2001.19.10.2754","article-title":"Phase I clinical trial of alitretinoin and tamoxifen in breast cancer patients: Toxicity, pharmacokinetic, and biomarker evaluations","volume":"19","author":"Lawrence","year":"2001","journal-title":"J. Clin. Oncol."},{"key":"ref_202","first-page":"1255","article-title":"Treatment with all-trans retinoic acid plus tamoxifen and vitamin E in advanced hepatocellular carcinoma","volume":"24","author":"Clerici","year":"2004","journal-title":"Anticancer Res."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"904","DOI":"10.2337\/dci22-0047","article-title":"Metformin and Cancer: Solutions to a Real-World Evidence Failure","volume":"46","author":"Yu","year":"2023","journal-title":"Diabetes Care"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1158\/1055-9965.EPI-14-0327","article-title":"The effect of metformin on mortality following cancer among patients with diabetes","volume":"23","author":"Lega","year":"2014","journal-title":"Cancer Epidemiol. Biomarker. Prev."},{"key":"ref_205","first-page":"683","article-title":"Metformin and cancer: An existing drug for cancer prevention and therapy","volume":"15","author":"Zi","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1192\/bjp.bp.116.181362","article-title":"Use of lithium and cancer risk in patients with bipolar disorder: Population-based cohort study","volume":"209","author":"Huang","year":"2016","journal-title":"Br. J. Psychiatry"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1056\/NEJMoa2012971","article-title":"Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia","volume":"383","author":"Dinardo","year":"2020","journal-title":"N. Engl. J. Med."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/33\/1\/25\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T05:21:33Z","timestamp":1767504093000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/33\/1\/25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,2]]},"references-count":207,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["curroncol33010025"],"URL":"https:\/\/doi.org\/10.3390\/curroncol33010025","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,2]]}}}