Finally, angiogenic signaling inhibitors include the modulation of mitogen-activated protein kinase (MAPK) and Akt signaling, inhibition of activator protein (AP)-1 activation, and the down-regulation of VEGF, transforming growth factor (TGF)-beta, MMP-9, as well as the upregulation of TIMP-1 which lead to reduction of tumor cell invasion and blood vessel growth [129], [130], [131], [132]. This evidence concerns the gene JUN and neoplasm.