The role of Notch signalling and its crosstalk with oestrogen receptor signalling in breast cancer - PubMed

6 hours ago

Notch signaling, crucial for mammary gland development, is often abnormally activated in breast cancer and contributes to cancer stem cell maintenance, EMT, angiogenesis, and metastasis.
Notch1 and Notch4 generally promote tumor aggressiveness in breast cancer, while Notch2 tends to have tumor-suppressive effects.
In ERα-positive breast cancer, ERα and Notch signaling work together to drive resistance to endocrine therapies.
In ERα-negative breast cancer, Notch signaling promotes stemness and angiogenesis independently.
Endocrine therapies can paradoxically activate Notch signaling, contributing to therapeutic resistance.
Co-targeting Notch alongside endocrine therapy is a proposed strategy to delay resistance, but pan-Notch inhibitors face toxicity issues.
New approaches, such as paralogue-specific antibodies, disrupting the transcription complex, rational drug combinations, and advanced delivery systems, are being developed to target Notch more selectively.

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