Tumour biology: herceptin acts as an anti-angiogenic cocktail.
Malignant tumours secrete factors that enable them to commandeer their own blood supply (angiogenesis), and blocking the action of these factors can inhibit tumour growth. But because tumours may become resistant to treatments that target individual angiogenic factors by switching over to other angiogenic molecules, a cocktail of multiple anti-angiogenic agents should be more effective. Here we show that herceptin, a monoclonal antibody against the cell-surface receptor HER2 (for human epidermal growth factor receptor-2; ref. 4), induces normalization and regression of the vasculature in an experimental human breast tumour that overexpresses HER2 in mice, and that it works by modulating the effects of different pro- and anti-angiogenic factors. As a single agent that acts against multiple targets, herceptin, or drugs like it, may offer a simple alternative to combination anti-angiogenic treatments.
Izumi
Yotaro
Y
Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Xu
Lei
L
di Tomaso
Emmanuelle
E
Fukumura
Dai
D
Jain
Rakesh K
RK
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D016228:Endothelial Growth Factors / Q000235:genetics; D015870:Gene Expression; D018734:Genes, erbB-2; D006801:Humans; D008222:Lymphokines / Q000235:genetics; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000235:genetics; D051379:Mice; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D000068878:Trastuzumab; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000068878:Trastuzumab