title: Combination therapy in cancer: effects of angiogenesis inhibitors on drug pharmacokinetics and pharmacodynamics.
abstract: Validated preclinical studies have provided evidence that anti-vascular endothelial growth factor (VEGF) compounds enhance the activity of subsequent antitumor therapy, but the mechanism of this potentiation is far from clear. The most widespread explanation is enhanced delivery of therapeutics due to vascular remodeling, lower interstitial pressure, and increased blood flow. While the antiangiogenic effects on vascular morphology have been fairly consistent in both preclinical and clinical settings, the improvement of tumor vessel function is debated. This review focuses on the effect of anti-VEGF therapy on tumor microenvironment morphology and functions, and its therapeutic benefits when combined with other therapies. The uptake and spatial distribution of chemotherapeutic agents into the tumor after anti-VEGF are examined.
authors.affiliation: Department of Oncology, IRCCS-Mario Negri Institute for Pharmacological Research, Via La Masa 19, 20156, Milan, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Fuso Nerini
authors.affiliation: Department of Oncology, IRCCS-Mario Negri Institute for Pharmacological Research, Via La Masa 19, 20156, Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Cesca
authors.affiliation: Department of Oncology, IRCCS-Mario Negri Institute for Pharmacological Research, Via La Masa 19, 20156, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bizzaro
authors.affiliation: Department of Oncology, IRCCS-Mario Negri Institute for Pharmacological Research, Via La Masa 19, 20156, Milan, Italy. raffaella.giavazzi@marionegri.it.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Giavazzi
mesh_terms: D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D059016:Tumor Microenvironment / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis inhibitors; Combination therapies; Drug delivery; Tumor microenvironment