Why FDA nod for vepdegestrant is a major shift in cancer therapy

The U.S. Food and Drug Administration has approved vepdegestrant, a therapy for patients with ESR1-mutated, ER-positive, HER2-negative advanced breast cancer. The approval is notable because it is the first FDA-approved treatment that uses PROTAC (proteolysis-targeting chimaera) technology—an approach that eliminates a disease-causing protein inside cells rather than merely blocking it.

The article explains how PROTACs function. Each PROTAC molecule is built to connect two components: it binds to a chosen target protein and simultaneously recruits an E3 ligase, a cellular enzyme involved in protein breakdown. Bringing these together triggers targeted protein degradation. Unlike conventional inhibitors, which often need to remain bound to the protein for prolonged periods, PROTACs can act repeatedly: once they induce degradation of the target, they are released and can initiate degradation again.