Neuro-astrocytic network in breast cancer brain metastases: Adaptive mechanisms and novel therapeutic targets

Int J Cancer. 2025 Jul 1;157(1):18-31. doi: 10.1002/ijc.35421. Epub 2025 Apr 1.

Abstract

Breast cancer brain metastases (BrM) are a common and fatal complication in advanced breast cancer patients, with the intricate brain microenvironment significantly limiting the efficacy of current therapeutic strategies. Recently, the neuro-astrocytic network, as a core component of the brain metastasis microenvironment, has garnered extensive attention for its pivotal role in supporting tumor adaptive growth. This review systematically outlines the adaptive mechanisms of the neuro-astrocytic network in BrM, including bidirectional interactions between tumor cells, neurons, and astrocytes, and their profound effects on synapse-like signaling, metabolic pathways, and regulatory networks. Furthermore, we integrate recent advancements in exploring therapeutic targets and discuss potential intervention strategies against tumor-microenvironment interactions and associated challenges. Future research focusing on the multi-target collaborative mechanisms within this network and its clinical translational potential may provide new avenues for precise treatment of BrM.

Keywords: breast cancer brain metastases; metabolic regulation; neuro–astrocytic network; signaling pathways; therapeutic targets.

Publication types

  • Review

MeSH terms

  • Animals
  • Astrocytes* / drug effects
  • Astrocytes* / metabolism
  • Astrocytes* / pathology
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / metabolism
  • Brain Neoplasms* / secondary
  • Breast Neoplasms* / pathology
  • Female
  • Humans
  • Molecular Targeted Therapy
  • Neurons* / metabolism
  • Neurons* / pathology
  • Signal Transduction
  • Tumor Microenvironment