{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T07:16:37Z","timestamp":1793085397210,"version":"4.5.0"},"reference-count":93,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"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":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Vascular tumours and malformations encompass infantile hemangiomas (IHs) and genetically driven vascular malformations with distinct natural histories and therapeutic vulnerabilities. The discovery that the non\u2010selective beta\u2010blocker propranolol induces rapid regression of proliferating IHs established the first widely adopted systemic pharmacologic therapy in vascular anomaly care and provided a clinical proof\u2010of\u2010concept that targeting lesion\u2010specific endothelial biology can alter disease course. In parallel, recurrent somatic variants affecting PI3K\/AKT\/mTOR (e.g., PIK3CA, TEK\/TIE2, AKT1) and RAS\/MAPK (e.g., KRAS, NRAS) signalling have reframed many malformations as mosaic disorders amenable to targeted inhibition with agents such as sirolimus, alpelisib, AKT inhibitors and MEK inhibitors. This review synthesizes translational mechanisms, clinical evidence and safety considerations for beta\u2010blockers and emerging targeted therapies, emphasizing lesion phenotype, timing of intervention and molecular stratification as determinants of response. We highlight current limitations, including toxicity, durability and pathway escape, and outline future directions for precision therapy and genotype\u2010guided trial design in vascular anomalies.<\/jats:p>","DOI":"10.1111\/jcmm.71103","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T05:01:33Z","timestamp":1775192493000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Targeted Therapies in Infantile Hemangiomas and Vascular Malformations: From \u03b2\u2010Blockers to\n                    <scp>PI3K<\/scp>\n                    \/\n                    <scp>AKT<\/scp>\n                    \/\n                    <scp>mTOR<\/scp>\n                    Inhibitors"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8042-3967","authenticated-orcid":false,"given":"Hubert","family":"Arasiewicz","sequence":"first","affiliation":[{"name":"Clinical Department of Pediatric Dermatology and Vascular Anomalies, Faculty of Medical Sciences in Katowice, Medical University of Silesia, John Paul II Children's and Family Health Center  Sosnowiec Silesian Voivodeship Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Dec","sequence":"additional","affiliation":[{"name":"Clinical Department of Pediatric Dermatology and Vascular Anomalies, Faculty of Medical Sciences in Katowice, Medical University of Silesia, John Paul II Children's and Family Health Center  Sosnowiec Silesian Voivodeship Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.17062"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14020425"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2022.10.047"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0000000000000496"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2015\u20100065"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc0708819"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1404710"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0000000000000238"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0000000000007699"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.2147\/CCID.S332625"},{"key":"e_1_2_16_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells13201674"},{"key":"e_1_2_16_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422\u2010020\u201000424\u20102"},{"key":"e_1_2_16_14_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2012.654"},{"key":"e_1_2_16_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25453"},{"issue":"1","key":"e_1_2_16_16_1","first-page":"48","article-title":"Propranolol Inhibits Angiogenesis via Down\u2010Regulating the Expression of Vascular Endothelial Growth Factor in Hemangioma Derived Stem Cell","volume":"7","author":"Zhang L.","year":"2013","journal-title":"International Journal of Clinical and Experimental Pathology"},{"key":"e_1_2_16_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apha.2017.08.002"},{"key":"e_1_2_16_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23095140"},{"key":"e_1_2_16_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2018690118"},{"key":"e_1_2_16_20_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S38403"},{"key":"e_1_2_16_21_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2018.9013"},{"key":"e_1_2_16_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11154539"},{"key":"e_1_2_16_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.985363"},{"key":"e_1_2_16_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2022.107110"},{"key":"e_1_2_16_25_1","doi-asserted-by":"publisher","DOI":"10.1001\/archoto.2011.1096"},{"key":"e_1_2_16_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201022\u20101366"},{"key":"e_1_2_16_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.117181"},{"key":"e_1_2_16_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17142364"},{"key":"e_1_2_16_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698\u2010019\u20100099\u20109"},{"key":"e_1_2_16_30_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.43026"},{"key":"e_1_2_16_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI151109"},{"key":"e_1_2_16_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440\u20101754.2012.02552.x"},{"key":"e_1_2_16_33_1","doi-asserted-by":"publisher","DOI":"10.11622\/smedj.2020008"},{"key":"e_1_2_16_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abd.2022.04.008"},{"key":"e_1_2_16_35_1","doi-asserted-by":"publisher","DOI":"10.2147\/TCRM.S291059"},{"key":"e_1_2_16_36_1","doi-asserted-by":"publisher","DOI":"10.4103\/ojo.ojo_11_22"},{"key":"e_1_2_16_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/srt.13310"},{"key":"e_1_2_16_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/ped.15278"},{"key":"e_1_2_16_39_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2021.0469"},{"key":"e_1_2_16_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/SCS.0000000000010001"},{"key":"e_1_2_16_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431\u2010025\u201005983\u20103"},{"key":"e_1_2_16_42_1","doi-asserted-by":"publisher","DOI":"10.12669\/pjms.40.2(ICON)0.8983"},{"key":"e_1_2_16_43_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2021.0596"},{"key":"e_1_2_16_44_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoto.2021.0454"},{"key":"e_1_2_16_45_1","doi-asserted-by":"publisher","DOI":"10.4103\/jiaps.jiaps_3_21"},{"key":"e_1_2_16_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdin.2023.02.001"},{"key":"e_1_2_16_47_1","doi-asserted-by":"publisher","DOI":"10.1159\/000536144"},{"key":"e_1_2_16_48_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoto.2021.0454"},{"key":"e_1_2_16_49_1","doi-asserted-by":"publisher","DOI":"10.1080\/03007995.2024.2318058"},{"key":"e_1_2_16_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2019.01.011"},{"key":"e_1_2_16_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvsv.2025.102284"},{"key":"e_1_2_16_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers9110152"},{"key":"e_1_2_16_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2014.164"},{"key":"e_1_2_16_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/targets2040020"},{"key":"e_1_2_16_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1549\u20108719.2009.00012.x"},{"key":"e_1_2_16_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12886\u2010022\u201002334\u2010w"},{"key":"e_1_2_16_57_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2015\u20103257"},{"key":"e_1_2_16_58_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.173095"},{"key":"e_1_2_16_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00405\u2010023\u201007991\u20101"},{"key":"e_1_2_16_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00405\u2010022\u201007378\u20108"},{"key":"e_1_2_16_61_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2021.3459"},{"key":"e_1_2_16_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13488"},{"key":"e_1_2_16_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.curtheres.2014.09.004"},{"key":"e_1_2_16_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.300"},{"key":"e_1_2_16_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/pde.14104"},{"key":"e_1_2_16_66_1","first-page":"20","article-title":"Sirolimus for the Treatment of Benign Vascular Anomalies in Children: A Single Centre Experience","volume":"28","author":"Tezol O.","year":"2023","journal-title":"Hong Kong J Paediatr (New Series)"},{"issue":"8","key":"e_1_2_16_67_1","doi-asserted-by":"crossref","first-page":"A320","DOI":"10.1016\/j.fander.2023.09.553","article-title":"Traitement d'un h\u00e9mangiome infantile r\u00e9sistant au propranolol par une courte cure de sirolimus","volume":"3","author":"Dekeuleneer V.","year":"2023","journal-title":"Annales de Dermatologie et de V\u00e9n\u00e9r\u00e9ologie"},{"key":"e_1_2_16_68_1","doi-asserted-by":"publisher","DOI":"10.4103\/jrpp.jrpp_58_25"},{"key":"e_1_2_16_69_1","doi-asserted-by":"publisher","DOI":"10.13181\/mji.cr.205036"},{"key":"e_1_2_16_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390\u2010025\u201004028\u20107"},{"key":"e_1_2_16_71_1","doi-asserted-by":"publisher","DOI":"10.6004\/jadpro.2020.11.7.9"},{"key":"e_1_2_16_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010018\u20100217\u20109"},{"key":"e_1_2_16_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010024\u201001862\u20109"},{"key":"e_1_2_16_74_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202115619"},{"key":"e_1_2_16_75_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-018-0540-1"},{"key":"e_1_2_16_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.01.015"},{"key":"e_1_2_16_77_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-021-01745-0"},{"key":"e_1_2_16_78_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw676"},{"key":"e_1_2_16_79_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/1726078"},{"key":"e_1_2_16_80_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.111.647982"},{"key":"e_1_2_16_81_1","doi-asserted-by":"publisher","DOI":"10.1080\/09546634.2019.1590521"},{"key":"e_1_2_16_82_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0903036"},{"key":"e_1_2_16_83_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010024\u201001978\u20100"},{"key":"e_1_2_16_84_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30056"},{"key":"e_1_2_16_85_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddac169"},{"key":"e_1_2_16_86_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202012324"},{"key":"e_1_2_16_87_1","doi-asserted-by":"publisher","DOI":"10.3233\/NPM\u2010200504"},{"key":"e_1_2_16_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.01.066"},{"key":"e_1_2_16_89_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2309160"},{"key":"e_1_2_16_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e19244"},{"key":"e_1_2_16_91_1","doi-asserted-by":"publisher","DOI":"10.1080\/09546634.2019.1687822"},{"key":"e_1_2_16_92_1","doi-asserted-by":"publisher","DOI":"10.2147\/CCID.S462665"},{"key":"e_1_2_16_93_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S460575"},{"key":"e_1_2_16_94_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010023\u201002364\u2010x"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.71103","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcmm.71103","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.71103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T09:13:20Z","timestamp":1776849200000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.71103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":93,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1111\/jcmm.71103"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.71103","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2026-02-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71103"}}