title: Inhibition of placenta growth factor with TB-403: a novel antiangiogenic cancer therapy.
abstract: BACKGROUND
  There is clinical evidence that therapies targeting the vascular endothelial growth factor pathway are effective in delaying cancer progression. However, tumors may be either intrinsically resistant or evolve resistance to such therapies. Hence, there is a need for new therapies targeting angiogenesis.
  
  
  METHODS
  The data are obtained by searching in the PubMed database. The search terms used included antiangiogenic therapy, TB-403 (RO5323441), placenta growth factor (PlGF) and VEGFR-1 (Flt-1). We review preclinical data concerning the function and inhibition of PlGF and summarize data on expression of PlGF in cancer patients. Data from early-phase clinical trials of TB-403 (RO5323441), a monoclonal antibody inhibiting PlGF, are discussed. Future development strategies, therapeutic potentials and limitations of TB-403 are further evaluated.
  
  
  CONCLUSIONS
  There are some conflicting data on the function of PlGF and the importance of its role in primary tumor growth. Data from some preclinical models of PlGF inhibition and early-phase clinical trials with TB-403 are, however, promising, although the true potential of the drug is yet to be determined. Further clinical development should be preceded by molecular studies in the context of well-designed preclinical models and/or small translational studies. Future challenges involve identifying predictive biomarkers.
authors.affiliation: Department of Oncology, University of Copenhagen, Herlev Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark. dornie01@heh.regionh.dk
authors.forename: Dorte Lisbet
authors.initials: DL
authors.lastname: Nielsen
authors.forename: Lisa
authors.initials: L
authors.lastname: Sengeløv
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; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000517:prevention & control*; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; C569915:TB-403