REVIEW article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Pathology
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1677481
Deciphering Organotropism Reveals Therapeutic Targets in Metastasis
Provisionally accepted- Cancer Research Group (CRG), Faculty of Medicine, Universidad de Las Américas, Quito, Ecuador
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Metastasis remains the principal cause of cancer-related mortality, yet its distribution across organs is far from random. Instead, tumor cells exhibit organotropism, a consistent preference for colonizing specific distant tissues, a phenomenon shaped by anatomical constraints, molecular crosstalk, and microenvironmental compatibility. Far beyond mere mechanical entrapment in vascular beds, metastatic dissemination reflects a coordinated interplay between tumor-intrinsic programs and organ-specific niches. Tumor-derived extracellular vesicles, cytokines, and matrix-remodeling enzymes actively precondition distant sites through pre-metastatic niche formation, creating permissive microenvironments primed for colonization. Simultaneously, tissue-specific immune landscapes, stromal compositions, and mechanical architectures determine the fate of disseminated tumor cells, whether they are eliminated, enter dormancy, or form macrometastases. Phenotypic plasticity, metabolic reprogramming, and immune evasion mechanisms equip subclones with the capacity to exploit these unique niches. Across cancer types, reproducible patterns of organotropic metastasis not only guide clinical surveillance and therapeutic stratification but also reveal vulnerabilities in the metastatic cascade. This review synthesizes emerging mechanistic insights across anatomical, immunological, and molecular domains to construct a comprehensive framework of organotropism, highlighting therapeutic opportunities to intercept metastasis at organ-specific checkpoints.
Keywords: metastasis, Organotropism, Pre-metastatic niche, phenotypic plasticity, metabolic reprogramming, Immune Evasion
Received: 31 Jul 2025; Accepted: 03 Oct 2025.
Copyright: © 2025 Bautista and López-Cortés. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Andrés López-Cortés, aalc84@gmail.com
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