Receptors found on cell surfaces bind to hormones, proteins, and other molecules, helping cells respond to their environment. MIT chemists have now discovered how one of these receptors changes its shape when it binds to its target, and how those changes trigger cells to grow and proliferate.

This receptor, known as epidermal growth factor receptor (EGFR), is overexpressed in many types of cancer and is the target of several cancer drugs. These drugs often work well at first, but tumors can become resistant to them. Understanding the mechanism of these receptors better may help researchers design drugs that can evade that resistance, says Gabriela Schlau-Cohen, an associate professor of chemistry at MIT.

“Thinking about more general mechanisms to target EGFR is an exciting new direction, and gives you a new avenue to think about possible therapies that may not evolve resistance as easily,” she says.

Schlau-Cohen and Bin Zhang, the Pfizer-Laubach Career Development Assistant Professor of Chemistry, are the senior authors of the study, which appears today in Nature Communications. The paper’s lead authors are MIT graduate student Shwetha Srinivasan and former MIT postdoc Raju Regmi.

Shape-changing receptors

The EGF receptor is one of many receptors that help control cell growth. Found on most types of mammalian epithelial cells, which line body surfaces and organs, it can respond to several types of growth factors in addition to EGF. Some types of cancer, especially lung cancer and glioblastoma, overexpress the EGF receptor, which can lead to uncontrolled growth.

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