Induction of complete regressions of oncogene-induced breast tumors in mice.
Over the past decade, mouse models of cancer have come to resemble human disease much more closely than simple subcutaneous or orthotopic systems. Intervention strategies that work on these new model systems are more likely to have an impact clinically. We have shown recently that antiangiogenic stress imposed by loss of Id protein in endothelial progenitor cells results in dramatic central necrosis in breast tumors initiated in mice by overexpression of the her2/neu oncogene. Tumor cells remain viable at the periphery, perhaps via the hypoxic response pathway which allows the lesions to expand. Inhibition of this pathway by the inactivation of the Hif-1alpha chaperone Hsp90 in combination with antiangiogenic stress leads to the first reported complete regression of these aggressive breast tumors.
Benezra
R
R
Department of Cancer Biology and Genetics Memorial Sloan-Kettering Cancer Center, New York 10021, USA.
Henke
E
E
Ciarrocchi
A
A
Ruzinova
M
M
Solit
D
D
Rosen
N
N
Nolan
D
D
Mittal
V
V
de Candia
P
P
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D016227:Benzoquinones / Q000627:therapeutic use; D015687:Cell Hypoxia; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D051796:Inhibitor of Differentiation Proteins / Q000172:deficiency / Q000235:genetics; D047029:Lactams, Macrocyclic / Q000627:therapeutic use; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000235:genetics* / Q000628:therapy*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic
D020533:Angiogenesis Inhibitors; D016227:Benzoquinones; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051796:Inhibitor of Differentiation Proteins; D047029:Lactams, Macrocyclic; C112765:tanespimycin