Targeting the Metabolic Niche: Vulnerabilities and Opportunities in Brain Metastases

Abstract

Brain metastases are the most common intracranial tumor in adults, and most arise from lung, breast, or melanoma. We propose a conceptual framework organized around three requirements for colonization, each unevenly distributed across the brain: vascular access, metabolic substrate, and escape from immune surveillance. We organize the literature around this three-axis framework and argue that metabolism, though the least exploited clinically, is where personalization may deliver the largest near-term gains. We review how lung, breast, and melanoma metastases each pair a characteristic metabolic program with characteristic anatomical distributions. Building on this, we discuss how targeted metabolic therapy, primary cancer-informed prediction, and longitudinal modeling can bring metabolism into precision brain metastasis care.