{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:40:31Z","timestamp":1791463231019,"version":"4.3.4"},"reference-count":87,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:00:00Z","timestamp":1712102400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Icaritin is a natural prenylated flavonoid derived from the Chinese herb Epimedium. The compound has shown antitumor effects in various cancers, especially hepatocellular carcinoma (HCC). Icaritin exerts its anticancer activity by modulating multiple signaling pathways, such as IL\u20106\/JAK\/STAT3, ER\u2010\u03b136, and NF\u2010\u03baB, affecting the tumor microenvironment and immune system. Several clinical trials have evaluated the safety and efficacy of icaritin in advanced HCC patients with poor prognoses, who are unsuitable for conventional therapies. The results have demonstrated that icaritin can improve survival, delay progression, and produce clinical benefits in these patients, with a favorable safety profile and minimal adverse events. Moreover, icaritin can enhance the antitumor immune response by regulating the function and phenotype of various immune cells, such as CD8+ T cells, MDSCs, neutrophils, and macrophages. These findings suggest that icaritin is a promising candidate for immunotherapy in HCC and other cancers. However, further studies are needed to elucidate the molecular mechanisms and optimal dosing regimens of icaritin and its potential synergistic effects with other agents. Therefore, this comprehensive review of the scientific literature aims to summarize advances in the knowledge of icaritin in preclinical and clinical studies as well as the pharmacokinetic, metabolism, toxicity, and mechanisms action to recognize the main challenge, gaps, and opportunities to develop a medication that cancer patients can use. Thus, our main objective was to clarify the current state of icaritin for use as an anticancer drug.<\/jats:p>","DOI":"10.1002\/ddr.22175","type":"journal-article","created":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T06:29:33Z","timestamp":1712125773000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["New insights into the anticancer therapeutic potential of icaritin and its synthetic derivatives"],"prefix":"10.1002","volume":"85","author":[{"given":"Octavio Daniel","family":"Reyes\u2010Hern\u00e1ndez","sequence":"first","affiliation":[{"name":"Laboratorio de Biolog\u00eda Molecular del C\u00e1ncer, UMIEZ, Facultad de Estudios Superiores Zaragoza Universidad Nacional Aut\u00f3noma de M\u00e9xico Ciudad de M\u00e9xico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Figueroa\u2010Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacogen\u00e9tica, UMIEZ, Facultad de Estudios Superiores Zaragoza Universidad Nacional Aut\u00f3noma de M\u00e9xico Ciudad de M\u00e9xico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8622-2004","authenticated-orcid":false,"given":"Laura Itzel","family":"Quintas\u2010Granados","sequence":"additional","affiliation":[{"name":"Colegio de Ciencias y Humanidades Plantel Cuautepec, Universidad Aut\u00f3noma de la Ciudad de M\u00e9xico. Ciudad de M\u00e9xico M\u00e9xico M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector","family":"Hern\u00e1ndez\u2010Parra","sequence":"additional","affiliation":[{"name":"Departamento de Farmacia, Facultad de Qu\u00edmica Universidad Nacional Aut\u00f3noma de M\u00e9xico Ciudad de M\u00e9xico Mexico"},{"name":"Departamento de Farmacolog\u00eda Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional (CINVESTAV\u2010IPN) Ciudad de M\u00e9xico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila I.","family":"Pe\u00f1a\u2010Corona","sequence":"additional","affiliation":[{"name":"Departamento de Farmacia, Facultad de Qu\u00edmica Universidad Nacional Aut\u00f3noma de M\u00e9xico Ciudad de M\u00e9xico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hern\u00e1n","family":"Cort\u00e9s","sequence":"additional","affiliation":[{"name":"Laboratorio de Medicina Gen\u00f3mica, Departamento de Gen\u00f3mica Instituto Nacional de Rehabilitaci\u00f3n Luis Guillermo Ibarra Ibarra Ciudad de Mexico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliya","family":"Kipchakbayeva","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Chemical Technology Al\u2010Farabi Kazakh National University Almaty Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhazira","family":"Mukazhanova","sequence":"additional","affiliation":[{"name":"Higher School of IT and Natural Sciences Sarsen Amanzholov East Kazakhstan University Ust\u2010Kamenogorsk Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solomon","family":"Habtemariam","sequence":"additional","affiliation":[{"name":"Pharmacognosy Research &amp; Herbal Analysis Services UK, Central Avenue, Chatham\u2010Maritime London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo","family":"Leyva\u2010G\u00f3mez","sequence":"additional","affiliation":[{"name":"Departamento de Farmacia, Facultad de Qu\u00edmica Universidad Nacional Aut\u00f3noma de M\u00e9xico Ciudad de M\u00e9xico Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietrich","family":"B\u00fcsselberg","sequence":"additional","affiliation":[{"name":"Weill Cornell Medicine\u2010Qatar, Education City, Qatar Foundation Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7301-8151","authenticated-orcid":false,"given":"Javad","family":"Sharifi\u2010Rad","sequence":"additional","affiliation":[{"name":"Facultad de Medicina Universidad del Azuay Cuenca Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,3]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3332\/ecancer.2015.536"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-01033-x"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2020.109124"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570163812666150602144310"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2014.01.004"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/395912"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2012.05.017"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclepro.2022.130903"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/nxz268"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10562-020-03522-3"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2013.31.15_suppl.2614"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.03.059"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.843489"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2019.102925"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1250042"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0071347"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2630"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0000000000000420"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2007.02.039"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/fsn3.1263"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.11.023"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2011.12.004"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/np300769c"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2020.1801892"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.28000"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.2c00908"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.enzmictec.2021.109940"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp300688t"},{"key":"e_1_2_13_30_1","first-page":"4628","article-title":"Icaritin induces apoptotic and autophagic cell death in human glioblastoma cells","volume":"8","author":"Li Z.","year":"2016","journal-title":"American Journal of Translational Research"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1039\/c1mb00001b"},{"key":"e_1_2_13_32_1","article-title":"Cytotoxic effect of Icaritin and its mechanisms in inducing apoptosis in human burkitt lymphoma cell line","volume":"2014","author":"Li Z. J.","year":"2014","journal-title":"BioMed Research International"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2015.11.006"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2004.06.021"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.993022"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2017.08.087"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1049\/htl2.12022"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.15205"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.4149\/gpb_2019041"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2011.01.001"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2014.1722"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113690"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.3762\/bjoc.11.135"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201308834"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202048905"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.2174\/157017861109140903103927"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871520616666160404111210"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00262"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.14641"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2016.11.027"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclepro.2017.09.192"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phytochem.2021.112895"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21708"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmrj.12116"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgv040"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2014.3007"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2021.39.15_suppl.4077"},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23147519"},{"key":"e_1_2_13_59_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00191"},{"key":"e_1_2_13_60_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.609295"},{"key":"e_1_2_13_61_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-15-0578"},{"key":"e_1_2_13_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep40894"},{"key":"e_1_2_13_63_1","first-page":"495","volume-title":"Pharmacognosy fundamentals, applications and strategies","author":"Turfus S. C.","year":"2017"},{"key":"e_1_2_13_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2015.06.006"},{"key":"e_1_2_13_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scib.2021.03.002"},{"key":"e_1_2_13_66_1","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2019.1628073"},{"key":"e_1_2_13_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2017.05.009"},{"key":"e_1_2_13_68_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28031109"},{"key":"e_1_2_13_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.12.059"},{"key":"e_1_2_13_70_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-015-0229-3"},{"key":"e_1_2_13_71_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2017.2906"},{"key":"e_1_2_13_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.07.071"},{"key":"e_1_2_13_73_1","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2022.2079769"},{"key":"e_1_2_13_74_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-022-02621-y"},{"key":"e_1_2_13_75_1","doi-asserted-by":"crossref","unstructured":"Yang J.\u2010G. Lu R. Ye X.\u2010J. Zhang J. Tan Y.\u2010Q. &Zhou G.(2017). Icaritin reduces oral squamous cell carcinoma progression via the inhibition of STAT3 signaling.International Journal of Molecular Sciences 18 132.","DOI":"10.3390\/ijms18010132"},{"key":"e_1_2_13_76_1","doi-asserted-by":"crossref","unstructured":"Yang X. J. Xi Y. M. &Li Z. J.(2019). Icaritin: A novel natural candidate for hematological malignancies therapy.BioMed Research International 2019 4860268.","DOI":"10.1155\/2019\/4860268"},{"key":"e_1_2_13_77_1","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2022.2147601"},{"key":"e_1_2_13_78_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13194"},{"key":"e_1_2_13_79_1","first-page":"5","article-title":"Antitumor effects of icaritin and the molecular mechanisms","volume":"29","author":"Zhang C.","year":"2020","journal-title":"Discovery Medicine"},{"key":"e_1_2_13_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104991"},{"key":"e_1_2_13_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2022.04.012"},{"key":"e_1_2_13_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2008.10.035"},{"key":"e_1_2_13_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2014.07.045"},{"key":"e_1_2_13_84_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5578"},{"key":"e_1_2_13_85_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7254.2005.00076.x"},{"key":"e_1_2_13_86_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023720"},{"key":"e_1_2_13_87_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3399"},{"key":"e_1_2_13_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phytol.2017.04.027"}],"container-title":["Drug Development Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.22175","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T21:13:16Z","timestamp":1760389996000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/ddr.22175"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4]]},"references-count":87,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1002\/ddr.22175"],"URL":"https:\/\/doi.org\/10.1002\/ddr.22175","archive":["Portico"],"relation":{},"ISSN":["0272-4391","1098-2299"],"issn-type":[{"value":"0272-4391","type":"print"},{"value":"1098-2299","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4]]},"assertion":[{"value":"2023-10-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e22175"}}