The EGFR, also known as ErbB1, is a 170 kDa protein belonging to the four-member ErbB family of transmembrane tyrosine kinase growth factor receptors. Binding by a number of ligands induces conformational alterations in the single chain receptor, allowing dimerization or oligomerization with other EGFR molecules or other members of the ErbB family. Multimer formation leads to asymmetric autophosphorylation of a tyrosine residue on the intracellular portion of one of the molecules, allowing the receptor to recruit docking proteins and signal transduction molecules. The resulting cascades, involving the Ras/mitogen-activating protein (MAP) kinase pathway, the Phosphoinositide-3 kinase (PI3K)/Akt pathway, Src family kinases, and signal transducers and activator of transcription (STAT) proteins, result in upregulation of mitogenic, antiapoptotic, angiogenic, and pro-invasive cellular mechanisms. EGFR is expressed or overexpressed in many cancers, Which make it a useful target for targeted therapies of cancers, such as breast cancer, colorectal cancer, head and neck cancer, non-small-cell lung cancer, ovivian cancer and pancreatic cancer.
Vascular endothelial growth factor (VEGF) is a key regulator of physiological angiogenesis during embryogenesis, skeletal growth and reproductive functions. VEGF has also been implicated in pathological angiogenesis associated with tumors, intraocular neovascular disorders and other conditions. The biological effects of VEGF are mediated by two receptor tyrosine kinases (RTKs), VEGFR-1 and VEGFR-2, which differ considerably in signaling properties. Non-signaling co-receptors also modulate VEGF RTK signaling. Currently, several VEGF inhibitors are undergoing clinical testing in several malignancies. VEGF inhibition is also being tested as a strategy for the prevention of angiogenesis, vascular leakage and visual loss in age-related macular degeneration.