The U.S. Food and Drug Administration has approved the first drug in a novel class of cancer therapies that works by destroying disease-causing proteins from within cells, marking a turning point for patients with a common form of advanced breast cancer. The once-daily oral medication, vepdegestrant, sold under the brand name Veppanu, is now available for adults with estrogen receptor-positive, HER2-negative breast cancer that carries an ESR1 mutation and has spread or cannot be surgically removed.
The approval is the culmination of more than a decade of research into PROTAC technology, short for Proteolysis Targeting Chimera. Unlike traditional drugs that block a protein’s activity, PROTACs work by tagging harmful proteins for destruction, essentially hijacking the cell’s natural recycling system. This approach was pioneered by Yale chemist Craig Crews, who founded the biotechnology company Arvinas in New Haven to develop the concept. In partnership with Pfizer, Arvinas brought vepdegestrant through clinical trials, and the FDA green light makes it the first PROTAC therapy ever approved for any disease.
Breast cancer remains the most common cancer among women worldwide, and many tumors rely on estrogen receptor signaling to grow. For patients whose disease has progressed despite other hormone-based treatments, vepdegestrant offers a new option. Crews noted that the approval carries personal weight: his own mother was diagnosed with breast cancer last year. “I’m thrilled that breast cancer patients will have an additional option for treatment,” he said.
How PROTACs Work and What Comes Next
The technology behind vepdegestrant emerged from Crews’s earlier work on proteasome inhibitors, drugs that block protein degradation. He later reversed that strategy, asking whether it was possible to force the cell to eliminate problematic proteins. That question led to the development of PROTACs, which were licensed to Arvinas in 2013. Since then, dozens of companies have launched programs exploring degraders for other cancers and even neurodegenerative diseases like dementia.
Crews sees the FDA approval as a catalyst for the entire field. “This first approval will encourage drug developers to explore the use of PROTACs for other diseases,” he said. His lab at Yale continues to work on the underlying science, and the journey from academic concept to approved medicine took roughly 25 years. “It has been extremely satisfying to take this idea from academic concept to FDA approval,” Crews added, “and demonstrates the continued need for supporting basic research, which is the underlying foundation for most of the exciting new drugs developed these days.” Patients and researchers alike now watch to see how this new class of therapies will reshape treatment for breast cancer and beyond.