EGFR signaling EGFR is really a transmembrane receptor tyrosine kinase that’s activated in a reaction to binding of ligands such as EGF, transforming growth factor, or amphiregulin. Ligand binding leads to receptor dimerization and activation of a number of downstream pathways which promote order Docetaxel angiogenesis, success, cell cycle progression, and change. There are several mechanisms through which EGFR inhibitors may connect to gemcitabine and/or radiation including cell cycle, EGF receptor action, and DNA repair. Along with nucleotide pool exhaustion, S phase arrest, and cell cycle checkpoint initial, gemcitabine stimulates phosphorylation of EGFR equally in head and neck along with in pancreas cancer cells. EGFR can be phosphorylated in response to various other cytotoxic agents and it’s hypothesized that phosphorylation might promote survival through stimulation of stress/survival response pathways as illustrated in Figure 3. This model provides an clear explanation for the improvement of EGFR inhibitors, including the little molecule tyrosine kinase inhibitor, erlotinib or even the anti Lymph node EGFR antibody, cetuximab to gemcitabine therapy. Preliminary studies in head and neck cancer xenografts demonstrated that gefitinib, which blocked gemcitabine mediated EGFR phosphorylation, enhanced gemcitabine mediated tumor growth delay. In other studies, both erlotinib and cetuximab were found to boost pancreas cyst growth delay when combined with radiation and gemcitabine. The power of EGFR inhibitors to sensitize to gemcitabine is sequence dependent. In head Lapatinib HER2 inhibitor and neck cancer cells as well as xenografts, the mixture of gemcitabine followed by gefitinib is better than the opposite sequence. This observation is supported in pancreatic cancer cells also where treatment with gemcitabine ahead of gefitinib produced additive to synergistic effects but antagonistic effects in a reaction to the reverse sequence. This schedule dependent cell killing may be due to the cell cycle effects of EGFR inhibitors since EGFR inhibitors up-regulate the cyclin dependent kinase inhibitors, p27 and p21 and hence make G1 cell cycle arrest. EGFR also plays a role in DNA repair. Ionizing radiation and chemotherapeutic agents create a selection of kinds of DNA damage including single and double strand DNA breaks, DNA adducts, and DNA crosslinks. EGFR can physically connect to DNA dependent protein kinase. In a reaction to light, EGFR translocates to the nucleus which is associated with increased DNA PK activity. Inhibition of EGFR activation by cetuximab blocks DNA PK activity, nuclear EGFR significance, and radiation-induced DNA damage repair, and triggers radiosensitization.