Seeing more nuance for a cancer therapy

A growing number of cancer drugs are designed to shut off epidermal growth factor receptor (EGFR), a protein known to be involved in a wide array of cellular processes including proliferation. Now, Yale researchers have answered a long-standing question about how EGFR can mediate so many diverse processes.

Scientists already knew that seven different growth factors bind to the receptor portion of the EGFR protein, each causing two receptor molecules to come together, turning on the active portion of the proteins. But researchers had been puzzled by how the binding of each growth factor causes different actions within the cell.

Mark A. Lemmon, Ph.D., David A. Sackler Professor of Pharmacology and co-director of the Cancer Biology Institute at Yale Cancer Center, and colleagues formed crystals of the EGFR protein to study its structure under different conditions. Different growth factors, they showed, cause EGFR’s receptor portions to assemble in slightly different ways, with variations in the timing and strength of the association—which the cell ‘reads out’ as different signals.

The discovery, published online in Cell on October 12, may lead to drugs that target EGFR in more nuanced ways, rather than simply shutting it off.