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Updated: Aug 15, 2025

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
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Published on: January 12, 2020

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Targeting Notch-Driven Cytokine Secretion: Novel Therapies for Triple Negative Breast Cancer

Wanda Marini1,2, Brooke E Wilson3,4, Michael Reedijk2,5

  • 1Division of General Surgery, University of Toronto, Toronto, Ontario, Canada.

DNA and Cell Biology
|December 29, 2022
PubMed

Insights

Triple negative breast cancer (TNBC) is aggressive, with limited success from immune checkpoint inhibition (ICI). Targeting Notch signaling may overcome resistance by reducing tumor-associated macrophages and improving immunotherapy effectiveness.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Triple negative breast cancer (TNBC) presents aggressive characteristics, including high recurrence rates and poor survival.
  • Current immune checkpoint inhibition (ICI) therapies offer limited benefits for TNBC patients.
  • Notch signaling is implicated as a key driver in TNBC progression.

Purpose of the Study:

  • To investigate the role of Notch signaling in TNBC.
  • To explore the relationship between Notch, IL1β, CCL2, and tumor-associated macrophages (TAMs).
  • To evaluate the potential of targeting Notch, IL1β, or CCL2 for combination immunotherapy in TNBC.

Main Methods:

  • Analysis of Notch signaling pathways in TNBC.
  • Assessment of IL1β and CCL2 expression driven by Notch.
  • Evaluation of TAM recruitment in response to these cytokines.
  • Exploration of therapeutic strategies targeting Notch, IL1β, or CCL2.

Main Results:

  • Notch signaling drives the expression of IL1β and CCL2 in TNBC.
  • IL1β and CCL2 contribute to TAM recruitment.
  • TAMs promote immune evasion and tumor progression in TNBC.
  • Targeting these pathways may reduce TAMs and overcome ICI resistance.

Conclusions:

  • Notch signaling is a critical factor in TNBC pathogenesis and immune evasion.
  • Targeting Notch, IL1β, or CCL2 presents a promising strategy to enhance combination immunotherapy for TNBC.
  • This approach could potentially improve treatment outcomes for patients with this aggressive breast cancer subtype.
Keywords:
Notch signalingimmunotherapytriple negative breast cancertumor microenvironment

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