Proteolysis-targeting chimeras (PROTACs)
- Medical Review: Nan Chen, MD
Proteolysis-targeting chimeras (PROTACs) are a type of hormonal therapy that interferes with the growth of hormone receptor-positive, HER2-negative, locally advanced or metastatic breast cancer.
Right now, there is one FDA-approved PROTAC to treat this kind of breast cancer. The cancer must have a mutation in a gene called ESR1.
How PROTACs work
When estrogen is present, estrogen receptors on breast cancer cells signal the cancer to grow and multiply. PROTACs work by attaching to estrogen receptors on breast cancer cells and marking them to be destroyed. Breast cancer cells then break the receptors down using their natural waste-disposal process.
Research has found that PROTACs can be especially helpful in treating locally advanced or metastatic hormone receptor-positive, HER2-negative breast cancer that has a mutation in the ESR1 gene. ESR1 mutations can make it harder for some types of hormonal therapy to work well. PROTACs can help overcome this treatment resistance by targeting estrogen receptors for removal.
There is one PROTAC approved to treat advanced breast cancers that have an ESR1 mutation. PROTACs are also being studied in breast cancers that do not have an ESR1 mutation.
PROTACs approved to treat breast cancer
There is one FDA-approved PROTAC available to treat breast cancer: vepdegestrant (Veppanu).
Vepdegestrant is approved to treat hormone receptor-positive, HER2-negative advanced or metastatic breast cancer that has an ESR1 gene mutation. It is a pill taken by mouth.
Learn more about vepdegestrant.
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Reviewed and updated: July 20, 2026
Reviewed by: Nan Chen, MD
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