TY - JOUR
T1 - Pathologic angiogenesis of malignant vascular sarcomas
T2 - Implications for treatment
AU - Ravi, Vinod
AU - Khan, Jalal A.
AU - Maki, Robert G.
N1 - Publisher Copyright:
Copyright © 2018 American Society of Clinical Oncology. All rights reserved.
PY - 2018/1/10
Y1 - 2018/1/10
N2 - Angiosarcoma, epithelioid hemangioendothelioma, and Kaposi sarcoma are classified according to the line of differentiation that these neoplastic cells most closely resemble: the endothelial cell. Although these malignant vascular sarcomas demonstrate immunohistochemical and ultrastructural features typical of this lineage, they vary dramatically in presentation and behavior, reflecting on-cologic mechanisms unique to each. Antineoplastic therapies offer significant benefit, but because of the rarity of these cancers, novel therapies are slow to develop, and treatment options for these cancers remain limited. Antiangiogenic approaches that have shown benefit in other malignancies have not fully realized their promise in vascular tumors, suggesting that these tumors do not depend entirely on either angiogenic growth factors or on neighboring endothelia that are affected by these agents. Nonetheless, translational studies have begun to unravel these distinct pathologies, identifying novel translocation products, targets of oncogenic virulence factors, and genomic mutations that hijack angiogenic signaling and drive malignant growth. Concurrently, an elaborate and highly regulated model of angiogenesis and lymphangiogenesis involving vascular endothelial growth factor–receptor tyrosine kinase and TGF-b and Notch pathways has emerged that informs treatment of these tumors as well as cancer in general. This review summarizes the literature on malignant vascular sarcomas in the context of current models of angiogenesis and, in light of recent clinical trial data, could help clinician-scientists generate novel therapeutic approaches.
AB - Angiosarcoma, epithelioid hemangioendothelioma, and Kaposi sarcoma are classified according to the line of differentiation that these neoplastic cells most closely resemble: the endothelial cell. Although these malignant vascular sarcomas demonstrate immunohistochemical and ultrastructural features typical of this lineage, they vary dramatically in presentation and behavior, reflecting on-cologic mechanisms unique to each. Antineoplastic therapies offer significant benefit, but because of the rarity of these cancers, novel therapies are slow to develop, and treatment options for these cancers remain limited. Antiangiogenic approaches that have shown benefit in other malignancies have not fully realized their promise in vascular tumors, suggesting that these tumors do not depend entirely on either angiogenic growth factors or on neighboring endothelia that are affected by these agents. Nonetheless, translational studies have begun to unravel these distinct pathologies, identifying novel translocation products, targets of oncogenic virulence factors, and genomic mutations that hijack angiogenic signaling and drive malignant growth. Concurrently, an elaborate and highly regulated model of angiogenesis and lymphangiogenesis involving vascular endothelial growth factor–receptor tyrosine kinase and TGF-b and Notch pathways has emerged that informs treatment of these tumors as well as cancer in general. This review summarizes the literature on malignant vascular sarcomas in the context of current models of angiogenesis and, in light of recent clinical trial data, could help clinician-scientists generate novel therapeutic approaches.
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U2 - 10.1200/JCO.2017.74.9812
DO - 10.1200/JCO.2017.74.9812
M3 - Review article
C2 - 29220293
AN - SCOPUS:85040562749
SN - 0732-183X
VL - 36
SP - 194
EP - 201
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 2
ER -