Selective estrogen receptor degraders

Selective Estrogen Receptor Degraders (SERDs) are a class of medications used in the treatment of estrogen receptor (ER) positive breast cancer. They function by binding to the estrogen receptor and promoting its degradation, thereby inhibiting the receptor's activity and reducing the growth of cancer cells that depend on estrogen for growth and survival.

Mechanism of Action

SERDs exert their therapeutic effect by directly interacting with the estrogen receptor. Unlike selective estrogen receptor modulators (SERMs), which can have both agonist and antagonist effects depending on the target tissue, SERDs act as pure antagonists on the estrogen receptor. Upon binding to the ER, SERDs induce a conformational change that targets the receptor for proteasomal degradation. This leads to a decrease in ER levels within the cell, effectively cutting off the signal that many breast cancers require for growth.

Clinical Use

Breast cancer is the most common indication for SERD therapy. Specifically, SERDs are used in the treatment of ER-positive breast cancer, which accounts for approximately 70% of all breast cancer cases. These drugs are particularly useful in cases where the cancer has become resistant to first-line treatments such as tamoxifen (a SERM) or aromatase inhibitors.

Examples of SERDs

• Fulvestrant is the most well-known SERD and is used in the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women. It is administered via injection.
• Newer SERDs are being developed and tested in clinical trials, aiming to be more effective and have better delivery methods compared to fulvestrant.

Side Effects

The side effects of SERDs can vary depending on the specific medication but may include:

• Injection site reactions (for injectable SERDs like fulvestrant)
• Nausea
• Fatigue
• Headache
• Hot flashes

Future Directions

Research is ongoing to develop oral SERDs that are as effective as injectable forms but more convenient for patients. Additionally, combining SERDs with other therapies, such as CDK4/6 inhibitors, is a promising area of research that could improve outcomes for patients with ER-positive breast cancer.

See Also

• Selective Estrogen Receptor Modulators (SERMs)
• Estrogen Receptor
• Breast Cancer Treatment
• Hormone Therapy for Breast Cancer