Cutaneous Angiosarcomas

TY - JOUR

T1 - Cutaneous Angiosarcomas

T2 - Molecular Pathogenesis Guides Novel Therapeutic Approaches

AU - Goerdt, Lea V

AU - Schneider, Stefan W

AU - Booken, Nina

N1 - © 2022 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.

PY - 2022/4

Y1 - 2022/4

N2 - Cutaneous angiosarcoma (CAS) is a highly aggressive cancer with a poor prognosis. Primary, spontaneous CAS (pCAS) and secondary, post-irradiation- or lymphedema-associated CAS (sCAS) are clinically, but also molecularly distinct. 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-omics 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 VEGFR1-3 such as bevacizumab and pazopanib, and β-adrenoreceptor blockers such as propranolol. Finally, immunotherapies are being developed including immune checkpoint inhibitors pembrolizumab and nivolumab as well as anti-RANKL antibody denosumab.

AB - Cutaneous angiosarcoma (CAS) is a highly aggressive cancer with a poor prognosis. Primary, spontaneous CAS (pCAS) and secondary, post-irradiation- or lymphedema-associated CAS (sCAS) are clinically, but also molecularly distinct. 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-omics 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 VEGFR1-3 such as bevacizumab and pazopanib, and β-adrenoreceptor blockers such as propranolol. Finally, immunotherapies are being developed including immune checkpoint inhibitors pembrolizumab and nivolumab as well as anti-RANKL antibody denosumab.

KW - Bevacizumab/therapeutic use

KW - Hemangiosarcoma/drug therapy

KW - Humans

KW - Immune Checkpoint Inhibitors

KW - Nivolumab/therapeutic use

KW - Skin Neoplasms/drug therapy

U2 - 10.1111/ddg.14694

DO - 10.1111/ddg.14694

M3 - SCORING: Review article

C2 - 35218306

VL - 20

SP - 429

EP - 443

JO - J DTSCH DERMATOL GES

JF - J DTSCH DERMATOL GES

SN - 1610-0379

IS - 4

ER -