title: Vascular disrupting agents (VDA) in oncology: advancing towards new therapeutic paradigms in the clinic.
abstract: Vascular Disrupting Agents (VDA) are a potential new class of oncology drugs that have garnered attention recently as a number of these agents have entered into Phase 2-3 studies. Currently available data suggest how the subsequent evolution of these agents into clinical practice may proceed, with new therapeutic paradigms based on similarities, differences and interactions with current standard of care agents. In particular, the broadly successful group of agents targeting angiogenesis through the Vascular Endothelial Growth Factor (VEGF) pathway, can be contrasted to the VDAs that principally disrupt established tumor vasculature through a different set of molecular targets. Although the angiogenesis inhibitors may benchmark where other vascularly targeted agents such as VDAs may be successful, the differences in terms of efficacy and safety profiles lead to important differentiation in how VDAs are likely to be used. Although the majority of VDAs bind tubulin, significant differences also exist between VDAs and cytotoxic agents, including tubulin targeted agents such as taxanes and vinca alkyloids. Clinical trial data is now available for several VDAs allowing such assessment. Data of yet has been the strongest in NSCLC, with indications of how these drugs may be developed beneficially in subsets of patients such as those with squamous cell histology or at risk of bleeding events. Other indications being aggressively pursued include prostate carcinoma, ovarian carcinoma, sarcomas and astrocytomas. The field also continues to advance with investigation into how to optimally schedule administration of VDAs and what effects might be class effects and/or markers of efficacy.
authors.affiliation: Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Spear
authors.forename: Patricia
authors.initials: P
authors.lastname: LoRusso
authors.forename: Alain
authors.initials: A
authors.lastname: Mita
authors.forename: Monica
authors.initials: M
authors.lastname: Mita
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects*; D002986:Clinical Trials as Topic; D054659:Diketopiperazines / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D012694:Serine / Q000031:analogs & derivatives / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D054659:Diketopiperazines; C514351:NPI 2358; D014404:Tubulin; D012694:Serine; C400245:AC 7700