Several types of cancers, such as ovarian, breast, lung and others, have been linked to the dysfunction of a particular family of cellular receptors (called the ErbB family) and the signaling pathways they regulate. Many chemotherapies target this dysfunction, in some cases successfully. But due to the various nuances in the pathway, many cancers remain unaffected by these therapies. New work from HSCI Principal Faculty Member Richard Lee demonstrates an unprecedented way to more effectively target the ErbB family and turn off their down-stream malignant characteristics, such as unchecked growth and cell migration. Typically, in malignant cell lines, the malignant ErbB signaling pathway is initiated when the various receptors in the family bind to individual “ligand” molecules. Lee and his group disrupted the pathway by introducing an influx of tethered ligands, which also bind to the receptors but do not initiate signaling. Standard ErbB-targeting chemotherapies, which utilize either small-molecule or antibody-based approaches, are limited by off-target toxicity and high dosing requirements. The new research from HSCI may introduce a safer and more effective treatment strategy to the playing field.

Jay, S.; Kurtagic, E.; Alvarez, L.; de Picciotto, S.; Sanchez, E,; Hawkins, J.; Prince, R.; Guerrero, Y.; Treasure, C.; Lee, R.; Griffith, L. (2011) Engineered Bivalent Ligands to Bias ErbB Receptor-Mediated Signaling and Phenotypes. Journal of Biological Chemistry Epub: 26 May 2011.