title: The Pleiotropic Role of L1CAM in Tumor Vasculature.
abstract: Angiogenesis, the formation of new vessels, is a key step in the development, invasion, and dissemination of solid tumors and, therefore, represents a viable target in the context of antitumor therapy. Indeed, antiangiogenic approaches have given promising results in preclinical models and entered the clinical practice. However, in patients, the results obtained so far with antiangiogenic drugs have not completely fulfilled expectations, especially because their effect has been transient with tumors developing resistance and evasion mechanisms. A better understanding of the mechanisms that underlie tumor vascularization and the functional regulation of cancer vessels is a prerequisite for the development of novel and alternative antiangiogenic treatments. The L1 cell adhesion molecule (L1CAM), a cell surface glycoprotein previously implicated in the development and plasticity of the nervous system, is aberrantly expressed in the vasculature of various cancer types. L1CAM plays multiple pro-angiogenic roles in the endothelial cells of tumor-associated vessels, thus emerging as a potential therapeutic target. In addition, L1CAM prevents the maturation of cancer vasculature and its inhibition promotes vessel normalization, a process that is thought to improve the therapeutic response of tumors to cytotoxic drugs. We here provide an overview on tumor angiogenesis and antiangiogenic therapies and summarize the current knowledge on the biological role of L1CAM in cancer vasculature. Finally, we highlight the clinical implications of targeting L1CAM as a novel antiangiogenic and vessel-normalizing approach.
authors.affiliation: Unit of Gynecological Oncology Research, European Institute of Oncology, Via G. Ripamonti 435, I-20141 Milan, Italy. francesca.angiolini@ieo.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Angiolini
authors.affiliation: Unit of Gynecological Oncology Research, European Institute of Oncology, Via G. Ripamonti 435, I-20141 Milan, Italy. ugo.cavallaro@ieo.it.
authors.forename: Ugo
authors.initials: U
authors.lastname: Cavallaro
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D058685:Genetic Pleiotropy; D006801:Humans; D009369:Neoplasms / Q000098:blood supply* / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism*; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D039842:Neural Cell Adhesion Molecule L1
keywords: L1CAM; antiangiogenic therapy; tumor angiogenesis; vascular normalization