title: Anti-angiogenic gene therapy of cancer: current status and future prospects.
abstract: The discovery of endogenous inhibitors of angiogenesis has made it possible to test the hypothesis that blocking the angiogenic switch may keep tumor growth in check, and has added a new investigational arm to the field of cancer gene therapy. Angiogenesis inhibitors are heterogeneous in origin and potency, and their growing list includes proteolysis products of larger molecules with a different function, such as angiostatin, endostatin and vasostatin, modulators of vascular endothelial growth factor activity, such as sFLT-1, and some cytokines/chemokines with marked anti-endothelial activity, such as IL-12, IFN-alpha, and CXCL10. Pre-clinical studies have clearly indicated that these factors are essentially cytostatic and that they need long-term administration in order to obtain prolonged anti-tumor effects, representing a rational basis for their delivery by a gene therapy approach. The experimental approaches attempted to date, reviewed herein, indicate overall that anti-angiogenic gene therapy has efficacy mainly as an early intervention strategy and that a better understanding of the biological mechanisms underlying resistance to angiogenesis inhibition, as well as appropriate combined treatments, are required to generate a conceptual advancement which could drive the field towards successful management of established tumors.
authors.affiliation: Department of Oncology and Surgical Sciences, Oncology Section, University of Padova, Via Gattamelata, 64, 35128 Padova, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Persano
authors.forename: Marika
authors.initials: M
authors.lastname: Crescenzi
authors.forename: Stefano
authors.initials: S
authors.lastname: Indraccolo
mesh_terms: D020533:Angiogenesis Inhibitors / Q000235:genetics* / Q000502:physiology; D000818:Animals; D005544:Forecasting; D018390:Gene Targeting / Q000639:trends; D005822:Genetic Vectors / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000628:therapy*
chemical_list: D020533:Angiogenesis Inhibitors