Estrogen-related receptor α in breast cancer: From molecular insights to targeted therapy

Area of Science:

• Oncology
• Molecular Biology
• Endocrinology

Background:

• Aggressive breast cancer subtypes like HER2-positive and triple-negative cancers present poor prognosis and frequent relapse, challenging current therapies.
• Estrogen-related receptor α (ERRα), an orphan nuclear receptor, is increasingly recognized for its role in regulating tumor metabolism and driving cancer progression.
• Overexpression of ERRα correlates with key indicators of malignancy, including epithelial-mesenchymal transition, angiogenesis, invasion, metastasis, and therapeutic resistance.

Purpose of the Study:

• To review the multifaceted roles of estrogen-related receptor α (ERRα) in the progression of various breast cancer subtypes.
• To highlight the potential of ERRα as a therapeutic target for improving outcomes in aggressive breast cancers.
• To consolidate current understanding of ERRα's involvement in tumor metabolism, metastasis, and treatment resistance.

Main Methods:

• Literature review of preclinical studies and existing research on estrogen-related receptor α (ERRα) in breast cancer.
• Analysis of the correlation between ERRα expression and aggressive breast cancer phenotypes, including metastasis and therapy resistance.
• Examination of the effects of ERRα inhibition (pharmacological or genetic) on oncogenic signaling and therapeutic sensitivity.

Main Results:

• Estrogen-related receptor α (ERRα) overexpression is prevalent in aggressive breast cancer subtypes and linked to poor prognosis.
• ERRα actively promotes tumor progression through regulation of energy metabolism, epithelial-mesenchymal transition, angiogenesis, invasion, and metastasis.
• Preclinical evidence indicates that targeting ERRα can suppress tumor growth and enhance sensitivity to existing therapies.

Conclusions:

• Estrogen-related receptor α (ERRα) is a critical driver of aggressive breast cancer phenotypes and therapeutic resistance.
• Targeting ERRα presents a promising therapeutic strategy for improving treatment outcomes in challenging breast cancer subtypes.
• Further investigation into ERRα's mechanisms and clinical translation is warranted for developing novel breast cancer therapies.