Estrogen Receptors and Enzymes Involved in Estrogen Synthesis as Breast Cancer Treatment Targets

Area of Science:

• Endocrinology
• Oncology
• Pharmacology

Background:

• Estrogens, especially 17β-estradiol (E2), are vital in breast cancer initiation and progression.
• Current treatments target estrogen receptors (ERs) or inhibit estrogen synthesis.
• Resistance to selective estrogen receptor modulators (SERMs) and inapplicability to triple-negative breast cancers (TNBCs) necessitate new therapeutic strategies.

Purpose of the Study:

• To review recent data on modulators/inhibitors of ERs and key enzymes in estrogen biosynthesis.
• To provide insights into the future development of anti-estrogen therapies for breast cancer.

Main Methods:

• Literature review of recent studies on ER modulators and estrogen biosynthesis enzyme inhibitors.
• Focus on aromatase, sulfatase, and 17β-hydroxysteroid dehydrogenases as drug targets.

Main Results:

• Selective estrogen receptor modulators (SERMs) are effective but face resistance and are unsuitable for TNBCs.
• Aromatase inhibitors are clinically used; sulfatase and 17β-hydroxysteroid dehydrogenase inhibitors are under investigation.
• Combined targeting of ERs and estrogen biosynthesis enzymes shows therapeutic promise.

Conclusions:

• Developing novel inhibitors targeting ERs and key estrogen biosynthesis enzymes is crucial for overcoming treatment resistance.
• Further research into sulfatase and 17β-hydroxysteroid dehydrogenase inhibitors is warranted.
• A multi-targeted approach may offer improved outcomes for various breast cancer subtypes.