EGFR-Targeted Approaches
{"Image DocumentName": "EGFR-Targeted Approaches", "Image ImageDescription": "TOXIN. There are a number of ways to target EGFR dysregulation. Antibodies against EGFR can act as receptor antagonists and prevent ligand binding, eg, cetuximab. Antibodies may prevent receptor dimerization, eg, trastuzumab (HER2). Antibodies against ligand also block binding, and this approach may be useful when 1 ligand binds to several receptors. Using a small molecule that specifically targets and either reversibly or irreversibly inhibits the tyrosine kinase activity is an approach that may block signaling by all active EGFR forms, including those receptors with mutated or deleted extracellular domains. Erlotinib and gefitinib are 2 ATP-competitive inhibitors of the EGFR tyrosine kinase. Mutations in the tyrosine kinase domain that lead to increased growth factor signaling correlate with increased clinical responsiveness to these TKIs. These mutations may result in increased sensitivity to erlotinib and gefitinib. Further prospective studies are required to better understand the prognostic and predictive value of EGFR tyrosine kinase domain mutations. Conjugates of a ligand and a cytotoxic agent (eg, TP-38 and DAB389EGF) or an antibody and a cytotoxic agent (eg, scFv-14e1-ETA fusion toxin) are another approach that may have the advantage of killing the cell after internalization, in addition to inhibiting tyrosine kinase activity. Anti-EGFR. blocking. antibodies. Antiligand. blocking. antibodies. Tyrosine. kinase. inhibitors. Ligand- toxin. conjugates. HER dimerization. inhibitors. Adapted from Noonberg and Benz. Drugs. 2000;59:753. Noonberg SB, Benz CC. Tyrosine kinase inhibitors targeted to the epidermal growth factor receptor subfamily: role as anticancer agents. Drugs. 2000;59: Erbitux\u00ae [package insert]. Branchburg, NJ, and Princeton, NJ: ImClone Systems and Bristol-Myers Squibb Company; Sampson JH, Akabani G, Archer G, et al. Clinical outcome and distribution measure of a recombinant chimeric protein composed of transforming growth factor alpha and a mutated Pseudomonas exotoxin (TP-38) via convection-enhanced microinfusion on a phase I study for malignant brain tumor. Proc Am Soc Clin Oncol. 2003;22:99. Abstract 397. Frankel AE, Liu TF, Thorburn AM, Tatter SB, Willingham MC. Recombinant toxin DAB389EGF produces regressions of human glioma xenografts in nude mice. Proc Am Soc Clin Oncol. 2004;23:220. Abstract Baselga J. Why the epidermal growth factor receptor? The rationale for cancer therapy. Oncologist. 2002;7(suppl 4):2-8.", "Image XResolution": "37", "Image YResolution": "37", "Image ResolutionUnit": "Pixels/Centimeter", "Image Software": "SlidePlayer", "Image YCbCrPositioning": "Centered"}