title: Anti-Angiogenic Drugs, Vascular Toxicity and Thromboembolism in Solid Cancer.
abstract: BACKGROUND
  Neo-angiogenesis, a key step in cancer progression, is a highly regulated process, in which Vascular Endothelial Growth Factor (VEGF) plays a fundamental role, thus representing the most suitable anti-angiogenic target. In the last year, a number of anti-VEGF drugs have been developed and approved for therapeutic use, especially in combination with standard chemotherapy. VEGF, however, is not only crucial for physiological and pathological angiogenesis, but also for the maintenance of vascular homeostasis, at a point that its pharmacological blockade may lead to endothelial dysfunction and adverse vascular effects, such as venous thromboembolism. The picture is further complicated by the understanding that the amount of VEGF production is influenced by genetic factors, with environmental ones accounting only for 20-30% of its variations. This has recently prompted the design of various pharmacogenetic studies to investigate the role of VEGF polymorphisms in determining the pharmacological response and safety profile of various anti-angiogenic drugs, suggesting that the analysis of VEGF genetic variants in cancer patients may further help personalize anti-angiogenic pharmacological strategies.
  
  
  CONCLUSIONS
  In this review, we initially focused on the biological mechanisms involved in vascular maintenance and angiogenesis. Then, discussed the efficacy and toxicity profile of some of the antiangiogenic drugs most commonly used in the treatment of solid cancer, with a particular focus on the thromboembolic complications of anti-angiogenic treatments in cancer patients. Finally, the impact of VEGF gene polymorphisms on clinical outcome and toxicity was briefly reviewed.
authors.affiliation: Department of Systems Medicine, Medical Oncology, Policlinico Tor Vergata Biospecimen Cancer Repository (PTV Bio.Ca.Re.), University of Rome Tor Vergata, Viale Oxford 81, 00133, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Riondino
authors.affiliation: Department of Palliative Care, San Raffaele Cassino, Clinical Center, Via Gaetano Di Biasio 1, 03043 Cassino (FR), Italy.
authors.forename: Girolamo
authors.initials: G
authors.lastname: Del Monte
authors.affiliation: Interinstitutional Multidisciplinary Biobank (BioBIM), IRCCS San Raffaele Pisana, Via di Val Cannuta 247, 00166 Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Fratangeli
authors.affiliation: Interinstitutional Multidisciplinary Biobank (BioBIM), IRCCS San Raffaele Pisana, Via di Val Cannuta 247, 00166 Rome, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Guadagni
authors.affiliation: Department of Systems Medicine, Medical Oncology, Policlinico Tor Vergata Biospecimen Cancer Repository (PTV Bio.Ca.Re.), University of Rome Tor Vergata, Viale Oxford 81, 00133, Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Roselli
authors.affiliation: Department of Human Sciences and Quality of Life Promotion, San Raffaele Roma Open University, Via di Val Cannuta 247, 00166, Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ferroni
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011110:Polymorphism, Genetic; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013923:Thromboembolism / Q000139:chemically induced* / Q000235:genetics; D042442:Vascular Endothelial Growth Factors / Q000235:genetics*; D000096662:Ramucirumab
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D047428:Protein Kinase Inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor; D011993:Recombinant Fusion Proteins; D042442:Vascular Endothelial Growth Factors; D000096662:Ramucirumab; C533178:aflibercept
keywords: Vascular endothelial growth factor; anti-angiogenic drugs; bevacizumab; solid cancer; thromboembolism; tyrosine kinase inhibitors