Tyrosine Kinase Receptor (RTK) families. Adapted by permission from Macmillan Publishers Ltd: The Biology of Cancer, Garland Science, 2007.

EGFR signaling pathways. Two important cell-survival pathways that operate downstream of activated ErbB transmembrane receptor tyrosine kinases (represented by pairs of yellow, and yellow and blue receptors to represent homo- and hetero-dimers, respectively), along with some of the key constituent signaling molecules are shown. The Ras-Raf-MEK-ERK pathway is shown on the left, and the phosphatidylinositol 3-kinase (PI3K)-AKT pathway is shown on the right. Key points along the pathway where targeted inhibition seems to exert a blockade are indicated by red circles, showing the relevant proteins they target. ERK, extracellular signal-regulated kinase; GRB2, growth factor receptor-bound protein 2; mTOR, mammalian target of rapamycin; SOS, son of sevenless. Used with permission from: Nature Reviews 2007 Sharma et al. Pg 177.

VEGF signaling pathways. Binding specificity of various vascular endothelial growth factor (VEGF) family members and their receptors. The VEGF family consists of seven ligands derived from distinct genes (VEGF-A, -B, -C, -D, and -E, placenta growth factor [PIGF] -1 and -2). VEGF family members have specific binding affinities to VEGF receptor (VEGFR) -1, VEGFR-2 and BEGFR-3 tyrosine kinase receptors as shown. In addition, neuropilin (NRP)-1 and NRP-2 are co-receptors for specific isoforms of VEGF family members and increase binding affinity of these ligands to their respective receptors. Used with permission from: Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 2005; 23: 1011–27.

EGFR signal transduction pathways. Three steps can be schematically defined in the activation of EGFR-dependent intracellular signaling. First, the binding of a receptor-specific ligand occurs in the extracellular portion of the EGFR or of one of the EGFR-related receptors (HER2, HER3, or HER4). Second, the formation of a functionally active EGFR-EGFR dimer (homodimer) or an EGFR-HER2, EGFR-HER3, or EGFR-HER4 dimer (heterodimer) causes the ATP-dependent phosphorylation of specific tyrosine residues in the EGFR intracellular domain. Third, this phosphorylation triggers a complex program of intracellular signals to the cytoplasm and then to the nucleus. The two major intracellular pathways activated by EGFR are the RAS-RAF-MEK-MAPK pathway, which controls gene transcription, cell-cycle progression from the G1 phase to the S phase, and cell proliferation, and the PI3K-Akt pathway, which activates a cascade of anti-apoptotic and prosurvival signals. bFGF, basic fibroblast growth factor, HB-EGF, heparin-binding EGF, MAPK, mitogen-activated protein kinase, PI3K, phosphatidylinositol 3,4,5-kinase, TGFa transforming growth factor alpha, and VEGF, vascular endothelial growth factor. Used with permission from: NEJM 2008 Ciardiello et al.).