Abstract
Antibody targeting of tumor-associated vasculature is a promising therapeutic approach in human cancer; however, a specific cell membrane marker for endothelial cells of tumor vasculature has not been discovered yet. Endoglin (CD105) is a cell-surface glycoprotein most recently identified as an optimal indicator of proliferation of human endothelial cells. The finding that CD105 is over-expressed on vascular endothelium in angiogenetic tissues has prompted several pre-clinical studies designed to get a deeper understanding on the role of CD105 in angiogenesis, and to evaluate the most appropriate clinical setting(s) to utilize CD105 as a therapeutic target. In this review, the foreseeable clinical applications of CD105 in human cancer are discussed.
Highlights
The availability of new and more sophisticated technologies, together with the improved knowledge on tumorhost interactions, have allowed the identification and characterization of different tumor-associated antigens (TAA) to be used as molecular targets for immunotherapeutic approaches in patients with solid or hematologic malignancies
Prompted by encouraging pre-clinical evidences, significant clinical results in cancer treatment have been obtained through antibody-based therapeutic regimens, such as those that target CD20 on malignant B cells [1] or HER2 in breast cancer [2]
Great interest is focused on angiogenesis and on its potential clinical implications in cancer, and vascular targeting represents a highly promising alternative to the direct engagement of therapeutic TAA on neoplastic cells [4,5]
Summary
The availability of new and more sophisticated technologies, together with the improved knowledge on tumorhost interactions, have allowed the identification and characterization of different tumor-associated antigens (TAA) to be used as molecular targets for immunotherapeutic approaches in patients with solid or hematologic malignancies. Among potential therapeutic strategies to induce tumor regression by blocking tumor blood supply, an intriguing approach relies on the selective targeting of cell surface molecules over-expressed on endothelial cells of tumor-associated blood vessels [4,5]. In this setting, emerging in vitro and in vivo pre-clinical evidence identifies CD105 as a cell membrane glycoprotein representing a prime vascular target to implement innovative antibodybased diagnostic and therapeutic strategies shared by human neoplasia of different histotype. CD105 and vascularization Even if its functional role is not fully understood, several findings suggest for the involvement of CD105 in angiogenesis and vascular development, and in maintaining vessel wall integrity
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