Exploring new pathways in endocrine-resistant breast cancer

Area of Science:

• Oncology
• Endocrinology
• Molecular Biology

Background:

• Hormone-dependent breast cancer (BC), including estrogen receptor-positive (ER+) and progesterone receptor-positive (PR+), comprises the luminal subtype.
• Endocrine therapy (ET) is the primary treatment for luminal BC, effectively reducing mortality and improving outcomes.
• Endocrine resistance is a significant clinical challenge, promoting cancer progression and limiting ET efficacy.

Purpose of the Study:

• To review established and novel pathways mediating endocrine therapy resistance in breast cancer.
• To focus on recently identified resistance mechanisms: RANKL/RANK, NFκB, and Notch signaling.
• To overview evidence for combined therapies and highlight future research directions.

Main Methods:

• Review of current clinical and preclinical data on endocrine resistance mechanisms in breast cancer.
• Focus on well-established pathways and three recently uncovered pathways (RANKL/RANK, NFκB, Notch).
• Analysis of evidence supporting combined therapies to overcome endocrine resistance.

Main Results:

• Several mechanisms of endocrine resistance in breast cancer have been identified and studied.
• Novel pathways including RANKL/RANK, NFκB, and Notch signaling are implicated in mediating resistance to endocrine therapy.
• Evidence supports the approval and use of combined therapies to overcome endocrine resistance.

Conclusions:

• Understanding endocrine resistance pathways is crucial for improving breast cancer treatment.
• Targeting novel pathways like RANKL/RANK, NFκB, and Notch may offer new therapeutic strategies.
• Future research into mediators of endocrine resistance is essential for developing novel treatment options for breast cancer.