Oral selective estrogen receptor degraders (SERDs): The new emperors in breast cancer clinical practice?

Area of Science:

• Oncology
• Endocrinology
• Pharmacology

Background:

• Endocrine therapy (ET) targeting estrogen receptor (ER) signaling is the standard treatment for ER-positive breast cancer (BC).
• Resistance to current ET, including aromatase inhibitors, tamoxifen, and fulvestrant, is a major cause of BC progression.
• Alterations in the ESR1 gene are frequently associated with acquired resistance to ET.

Purpose of the Study:

• To review the development of oral selective estrogen receptor degraders (SERDs).
• To summarize the current status and future perspectives of oral SERDs in overcoming ET resistance.
• To highlight the potential of oral SERDs in managing ER-positive BC with ESR1 mutations.

Main Methods:

• Review of recent scientific literature on ER-targeting therapies.
• Analysis of drug development pathways for novel oral SERDs.
• Evaluation of clinical data on the efficacy of oral SERDs against ESR1 mutations.

Main Results:

• New oral SERDs effectively reduce ER protein expression and block ER signaling.
• These agents demonstrate broader activity against various ESR1 mutations compared to existing therapies.
• Oral SERDs represent a promising strategy to overcome both de novo and acquired ET resistance.

Conclusions:

• Oral SERDs are emerging as a significant advancement in the treatment of ER-positive breast cancer.
• They offer a potential solution for patients who have developed resistance to standard endocrine therapies.
• Further research and clinical trials are essential to establish the full therapeutic role of oral SERDs.