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Epidermal growth factor-like domain-containing protein 7 (EGFL7) is a secreted protein that is highly expressed by endothelial cells during periods of active vascular growth, such as embryogenesis and tumor-induced angiogenesis [1, 3]. It primarily localizes to the extracellular matrix (ECM) at the EGFL7–endothelial cell interface, where it regulates the spatial organization of cells during blood vessel formation and maintains vascular integrity [3, 4]. EGFL7 functions by modulating the Notch signaling pathway and interacting with integrins, specifically alpha-v beta-3, to facilitate endothelial cell migration and tubulogenesis [1, 4]. In the context of oncology, EGFL7 is frequently overexpressed in various solid tumors, contributing to the development of a robust vascular network that supports tumor growth and metastasis [4, 5]. Therapeutic targeting of the EGFL7–endothelial cell interface, most notably with the humanized monoclonal antibody parsatuzumab, aims to inhibit these pro-angiogenic signals [2, 5]. While parsatuzumab was designed to enhance the efficacy of anti-VEGF therapies by disrupting vascular remodeling, clinical trials in metastatic colorectal cancer and non-small cell lung cancer have struggled to demonstrate a significant improvement in progression-free survival [2, 5].
Monoclonal antibody-mediated inhibition of EGFL7 binding to the extracellular matrix and endothelial cell receptors, disrupting vascular remodeling and angiogenesis.
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