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Myc amplification\/overexpression is a characteristic, although not exclusive feature of sCAS, while loss of TP53 selectively occurs in pCAS. Detailed molecular analyses with modern multi\u2010omics approaches have revealed that both pCAS and sCAS exhibit considerable molecular heterogeneity. Affected genes and their molecular regulators including a plethora of microRNAs may serve as future drug targets. Furthermore, pCAS could be subdivided into clusters with high tumor mutational burden and\/or high tumor inflammation signatures providing a rationale for the stratification of pCAS patients in future immunotherapeutic clinical studies. Development of novel treatment regimens guided by these molecular alterations, however, cannot fully keep up with the pace of their discovery due to the low incidence of the disease. Nevertheless, beyond conventional surgery and chemoradiotherapy, clinical trials investigating novel treatment options have been initiated including targeted therapies against VEGF and VEGFR1\u20133 such as bevacizumab and pazopanib, and \u03b2\u2010adrenoreceptor blockers such as propranolol. Finally, immunotherapies are being developed including immune checkpoint inhibitors pembrolizumab and nivolumab as well as anti\u2010RANKL antibody denosumab.<\/jats:p>","DOI":"10.1111\/ddg.14694","type":"journal-article","created":{"date-parts":[[2022,2,26]],"date-time":"2022-02-26T07:15:03Z","timestamp":1645859703000},"page":"429-443","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Cutaneous Angiosarcomas: Molecular Pathogenesis Guides Novel Therapeutic Approaches"],"prefix":"10.1111","volume":"20","author":[{"given":"Lea V.","family":"Goerdt","sequence":"first","affiliation":[{"name":"Department of Dermatology and Venereology University Medical Center Hamburg\u2010Eppendorf (UKE)  Hamburg Germany"},{"name":"Asklepios Campus Hamburg Medical Faculty Semmelweis University Budapest  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan W.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology University Medical Center Hamburg\u2010Eppendorf (UKE)  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Booken","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology University Medical Center Hamburg\u2010Eppendorf (UKE)  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2019.07.024"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.12312"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cup.13912"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1383"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2010.03484.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001398"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090637"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2013.163"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07739-0"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13981"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.21943"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms161025377"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1684\/ejd.2017.3084"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11252"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-1262"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5936"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-0418"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2921"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2020.151597"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/cup.13024"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jso.20766"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.111770"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13379"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13337"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.12.052"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI139080"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1101\/mcs.a004408"},{"key":"e_1_2_9_29_1","doi-asserted-by":"crossref","unstructured":"VogtT M\u00fcllerCSM MelchiorPet\u00a0al.S1\u2010Leitlinie Kutane Angiosarkome \u2013 Update 2021. 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