Details

Autor(en) / Beteiligte

• Xiong, Shuangshuang
• Song, Ke
• Xiang, Hua
• Luo, Guoshun

Titel

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

Ist Teil von

• European journal of medicinal chemistry, 2024-04, Vol.270, p.116393-116393, Article 116393

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• Estrogen receptor alpha (ERα), a nuclear transcription factor, is a well-validated therapeutic target for more than 70% of all breast cancers (BCs). Antagonizing ERα either by selective estrogen receptor modulators (SERMs) or selective estrogen receptor degraders (SERDs) forms the foundation of endocrine therapy and has achieved great success in the treatment of ERα positive (ERα+) BCs. Unfortunately, despite initial effectiveness, endocrine resistance eventually emerges in up to 30% of ERα+ BC patients and remains a significant medical challenge. Several mechanisms implicated in endocrine resistance have been extensively studied, including aberrantly activated growth factor receptors and downstream signaling pathways. Hence, the crosstalk between ERα and another oncogenic signaling has led to surge of interest to develop combination therapies and dual-target single agents. This review briefly introduces the synergisms between ERα and another anticancer target and summarizes the recent advances of ERα-based dual-targeting inhibitors from a medicinal chemistry perspective. Accordingly, their rational design strategies, structure-activity relationships (SARs) and biological activities are also dissected to provide some perspectives on future directions for ERα-based dual target drug discovery in BC therapy. [Display omitted] •The recent development of ERα-based dual inhibitors is reviewed for the first time.•Development of ERα-based inhibitors with dual-targeting capabilities were summarized.•The rational design strategies and biological activities were discussed.•Potential of ERα-based dual inhibitors for the treatment of Endocrine Resistant Breast Cancer.