Targeting HER1/EGFR: a molecular approach to cancer therapy.
The varying efficacy and toxicity of traditional cancer therapies has driven the development of novel target-based agents. Members of the HER (Human Epidermal Receptor) family, in particular epidermal growth factor receptor (HER1/EGFR), are attractive therapeutic targets because they are overexpressed and/or dysregulated in many solid tumors. Activation of HER1/EGFR mediated through ligand binding triggers a network of signaling processes that promote tumor cell proliferation, migration, adhesion, and angiogenesis, and decrease apoptosis. Therefore, inhibiting HER1/EGFR activity could effectively block downstream signaling events and, consequently, tumorigenesis. Various approaches are being investigated to target members of the HER family, particularly HER1/EGFR and HER2. At the forefront are monoclonal antibodies and small molecules that inhibit the receptor tyrosine kinase activity. Monoclonal antibodies have been developed that act against HER1/EGFR and HER2. Monoclonal antibodies block ligand binding and prevent ligand-induced activation. Tyrosine kinase inhibitors block receptor phosphorylation, preventing downstream signal transduction. Several HER1/EGFR-targeted agents are advanced in clinical development and attention is focused on optimizing their clinical use. While this process may prove challenging, it promises to be beneficial.
Arteaga
Carlos
C
Division of Oncology, Vanderbilt University School of Medicine, 2220 Pierce Avenue, 777 PRB, Nashville, TN 37232-6307, USA.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D020893:Receptor, ErbB-3 / Q000037:antagonists & inhibitors; D066247:Receptor, ErbB-4; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D008024:Ligands; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; C587689:ERBB4 protein, human