Metastatic Niches Uncovered: Organ-Specific Mechanisms Driving Brain, Bone, Lung, and Liver Metastases

Metastasis remains the leading cause of cancer-related death, yet therapeutic progress continues to lag behind advances in our understanding of primary tumor biology. Growing evidence shows that metastatic spread is not a uniform process but is heavily influenced by organ-specific microenvironments, or metastatic “niches.” Unique biological, immunological, and metabolic characteristics within the brain, bone, lung, and liver actively affect tumor colonization, survival, and growth.Recent breakthroughs have emphasized the importance of immune-glial cell communication in brain metastases, mechanisms like eIF4A in lung and liver metastasis, mitochondrial DNA-driven signaling related to metastatic fitness, and oxygenation-driven adaptation in bone metastases. Collectively, these discoveries mark a shift from viewing metastasis as a late-stage event to understanding it as a dynamic, targetable process driven by host-tumor interactions.Despite these advances, the field lacks a unified perspective that integrates new concepts across different organ systems and translates mechanistic insights into therapeutic opportunities.This Research Topic aims to:Synthesize emerging biological insights into organ-specific metastatic mechanismsHighlight common principles and key differences across brain, bone, lung, and liver metastasesIdentify translational vulnerabilities that could guide the development of next-generation, site-specific anti-metastatic therapies.In doing so, it aims to provide authors and readers with a conceptual framework for understanding how the metastatic niche influences disease progression and treatment response.This Research Topic will focus on the following interrelated themes:Brain Metastasesi) Immune-glial-tumor cell interactionsii) Blood–brain barrier dynamics and immune evasionBone Metastasesi) Hypoxia and oxygenation gradients influencing metastatic adaptationii) Crosstalk between tumor cells and osteoblast/osteoclast systemsLung and Liver Metastasesi) Translational regulation and the role of eIF4Aii) Metabolic plasticity and stress adaptation in highly vascular organsCross-Cutting Mechanismsi) Mitochondrial DNA signaling and metabolic reprogrammingii) Microenvironment-driven therapeutic resistanceiii) Opportunities for niche-targeted interventionRelevance and ContributionThis Research Topic aims toBring together original research and review articles that advance our collective understanding of organ-specific metastatic biology,Bridge basic mechanistic discovery with clinical relevanceServe as a roadmap for future research aimed at disrupting metastatic niches rather than treating metastases as biologically uniform entities.By framing metastasis through an organ-specific lens, this Research Topic will underscore how integrating microenvironmental biology into therapeutic design may unlock new strategies to prevent or control metastatic disease.Intended AudienceCancer biologists and translational researchersMedical oncologists and clinician-scientistsPharmaceutical and drug development scientistsEarly-career investigators seeking conceptual guidance in metastasis researchPlease note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal. Topic editors: Subhasis Das, Surya Kanta Dey, Ranabir Majumder Source: https://www.frontiersin.org/research-topics/80142/metastatic-niches-uncovered-organ-specific-mechanisms-driving-brain-bone-lung-and-liver-metastases