title: Tumour vasculature targeting agents in hybrid/conjugate drugs.
abstract: Tumour vasculature targeting has been a very active area of cancer drug discovery over the last decade. Growth of solid tumours beyond a certain point requires a sufficient blood supply in order for them to develop and metastasise. While novel anti-angiogenic and vascular disrupting agents represent an important contribution to the armoury of anti-cancer agents they nevertheless usually require combination with standard cytotoxic therapy in order to demonstrate positive clinical outcomes. In line with this consensus, a new concept has arisen, namely the design of functional hybrids where at least one component of the design targets a tumour angiogenic/vasculature pathway. This review will outline examples of such hybrid/conjugate-based approaches. Emphasis will be placed on their preclinical evaluation with particular focus on the RGD/NGR-conjugates, heparin-related hybrids and antibody-drug conjugates. In conclusion, the benefits and shortcomings of hybrids under development will be discussed in the context of future directions and applications.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: E M
authors.initials: EM
authors.lastname: Prokopiou
authors.forename: S A
authors.initials: SA
authors.lastname: Ryder
authors.forename: J J
authors.initials: JJ
authors.lastname: Walsh
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D008954:Models, Biological; D015394:Molecular Structure; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*
chemical_list: D020533:Angiogenesis Inhibitors