CAFs and Endocrine Therapy Resistance in Hormone Receptor-Positive Breast Cancer

Area of Science:

• Oncology
• Cancer Biology
• Endocrinology

Background:

• Endocrine resistance is a major challenge in treating hormone receptor-positive breast cancer.
• The tumor microenvironment (TME), particularly cancer-associated fibroblasts (CAFs), significantly contributes to endocrine therapy resistance.
• Specific CAF subtypes (e.g., CD146-negative, CD63-positive) and mechanisms like aberrant signaling pathways, epigenetic modifications (lncRNAs, miRNAs), and paracrine signaling are implicated.

Purpose of the Study:

• To explore the role of CAFs in endocrine resistance in breast cancer.
• To understand the mechanisms by which CAFs mediate resistance to endocrine therapies.
• To review current and emerging strategies for targeting CAFs in combination with endocrine therapy.

Main Methods:

• Literature review and synthesis of current research on CAFs and endocrine resistance.
• Analysis of proposed mechanisms including CAF subtypes, signaling pathways, and epigenetic factors.
• Examination of therapeutic strategies targeting CAFs and endocrine signaling.

Main Results:

• CAFs, through diverse mechanisms including specific subtypes and molecular signaling, promote endocrine resistance in breast cancer.
• Epigenetic modifications like lncRNAs and miRNAs within CAFs are key mediators.
• Simultaneous targeting strategies, such as FGFR inhibition combined with endocrine therapy, are under investigation.

Conclusions:

• CAFs are critical players in endocrine resistance, necessitating their targeting for effective treatment.
• The heterogeneity of CAFs presents a significant challenge for developing targeted therapies.
• Combined therapeutic approaches targeting both CAFs and endocrine signaling are a promising avenue for overcoming resistance in luminal breast cancer.