Dual-target inhibitors based on ERα: Novel therapeutic approaches for endocrine resistant breast cancer

Area of Science:

• Oncology
• Medicinal Chemistry
• Molecular Biology

Background:

• Estrogen receptor alpha (ERα) is a key target in over 70% of breast cancers (BCs).
• Endocrine therapies (SERMs, SERDs) targeting ERα are foundational but face emergent resistance in up to 30% of patients.
• Mechanisms of resistance involve aberrant signaling pathways, highlighting the need for combination strategies.

Purpose of the Study:

• To review the synergistic interactions between ERα and other anticancer targets.
• To summarize recent advances in ERα-based dual-targeting inhibitors from a medicinal chemistry viewpoint.
• To provide perspectives on future drug discovery for ERα-positive BC therapy.

Main Methods:

• Literature review focusing on medicinal chemistry and drug discovery.
• Analysis of rational design strategies for dual-targeting inhibitors.
• Examination of structure-activity relationships (SARs) and biological activities.

Main Results:

• Identified significant crosstalk between ERα and other oncogenic signaling pathways.
• Highlighted the development of novel ERα-based dual-targeting agents.
• Dissected design principles, SARs, and efficacy of these inhibitors.

Conclusions:

• Dual-targeting inhibitors offer a promising strategy to overcome endocrine resistance in ERα-positive breast cancer.
• Further research into rational design and SARs is crucial for developing effective combination therapies.
• ERα-based dual-target drug discovery holds potential for improved BC treatment outcomes.