title: Anti-angiogenic Therapy in Cancer: Downsides and New Pivots for Precision Medicine.
abstract: Primary solid tumors originate close to pre-existing tissue vasculature, initially growing along such tissue blood vessels, and this phenomenon is important for the metastatic potential which frequently occurs in highly vascularized tissues. Unfortunately, preclinic and clinic anti-angiogenic approaches have not been very successful, and multiple factors have been found to contribute to toxicity and tumor resistance. Moreover, tumors can highlight intrinsic or acquired resistances, or show adaptation to the VEGF-targeted therapies. Furthermore, different mechanisms of vascularization, activation of alternative signaling pathways, and increased tumor aggressiveness make this context even more complex. On the other hand, it has to be considered that the transitional restoration of normal, not fenestrated, microvessels allows the drug to reach the tumor and act with the maximum efficiency. However, these effects are time-limited and different, depending on the various types of cancer, and clearly define a specific "normalization window." So, new horizons in the therapeutic approaches consist on the treatment of the tumor with pro- (instead of anti-) angiogenic therapies, which could strengthen a network of well-structured blood vessels that facilitate the transport of the drug.
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania Catania, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Lupo
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania Catania, Italy.
authors.forename: Nunzia
authors.initials: N
authors.lastname: Caporarello
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania Catania, Italy.
authors.forename: Melania
authors.initials: M
authors.lastname: Olivieri
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania Catania, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Cristaldi
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania Catania, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Motta
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania Catania, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bramanti
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania Catania, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Avola
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania Catania, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Salmeri
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania Catania, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.affiliation: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania Catania, Italy.
authors.forename: Carmelina D
authors.initials: CD
authors.lastname: Anfuso
keywords: anti-angiogenic therapy; hypoxia detection; microvascular architecture; pericytes; tumor angiogenesis; tumor endothelial cells (TECs); vascular normalization