Hormonal and neuronal interactions shaping the brain metastatic microenvironment.

Area of Science:

• Neuroscience
• Oncology
• Endocrinology

Background:

• Metastatic progression, particularly to the central nervous system (CNS), is a leading cause of cancer mortality.
• Brain metastases (BrM) from lung, breast, and melanoma cancers have poor prognoses, despite advances in treating extracranial tumors.
• The increasing incidence of BrM highlights gaps in understanding CNS tumor biology and colonization.

Purpose of the Study:

• To review the hormonal landscape of the adult brain in the context of cancer neuroscience.
• To examine how neuroendocrine-immune interactions, influenced by sex hormones, may promote metastatic growth within the CNS.
• To identify novel therapeutic opportunities by understanding the interplay between hormones and tumor adaptation.

Main Methods:

• Literature review of existing research on brain metastases, cancer neuroscience, and hormonal regulation in the CNS.
• Analysis of the role of sex steroids and neurosteroids in the brain microenvironment.
• Exploration of neuroendocrine-immune interactions and their influence on tumor growth.

Main Results:

• Steroid hormones can cross the blood-brain barrier or be synthesized within the CNS, affecting inflammation, synaptic plasticity, and immune surveillance.
• Hormonal pathways normally involved in brain function may be co-opted by cancer cells to support colonization and growth.
• The interplay between systemic hormones, local steroidogenesis, and tumor adaptation is crucial for BrM development.

Conclusions:

• Understanding the brain's hormonal milieu is critical for addressing the challenges of brain metastases.
• Neuroendocrine-immune pathways represent promising targets for novel therapeutic strategies against BrM.
• Further research into hormone-tumor interactions in the CNS can lead to improved patient outcomes.