Cancer metastasis: molecular mechanisms and therapeutic interventions

Abstract The metastatic cascade is a complicated process where cancer cells travel across multiple organs distant from their primary site of onset. Despite the wide acceptance of the ‘seed and soil’ theory, mechanisms driving metastasis organotropism remain mystery. Using breast cancer of different...

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Main Authors: Xiaofeng Dai, Ming Xi, Jitian Li
Format: Article
Language:English
Published: Springer 2025-04-01
Series:Molecular Biomedicine
Subjects:
Online Access:https://doi.org/10.1186/s43556-025-00261-y
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author Xiaofeng Dai
Ming Xi
Jitian Li
author_facet Xiaofeng Dai
Ming Xi
Jitian Li
author_sort Xiaofeng Dai
collection DOAJ
description Abstract The metastatic cascade is a complicated process where cancer cells travel across multiple organs distant from their primary site of onset. Despite the wide acceptance of the ‘seed and soil’ theory, mechanisms driving metastasis organotropism remain mystery. Using breast cancer of different subtypes as the disease model, we characterized the ‘metastatic profile of cancer cells’ and the ‘redox status of the organ microenvironment’ as the primary determinants of cancer metastasis organotropism. Mechanically, we identified a positive correlation between cancer metabolic plasticity and stemness, and proposed oxidative stress as the selection power of cancer cells succeeding the metastasis cascade. Therapeutically, we proposed the use of pro-oxidative therapeutics in ablating cancer cells taking advantages of this fragile moment during metastasis. We comprehensively reviewed current pro-oxidative strategies for treating cancers that cover the first line chemo- and radio-therapies, approaches relying on naturally existing power including magnetic field, electric field, light and sound, nanoparticle-based anti-cancer composites obtained through artificial design, as well as cold atmospheric plasma as an innovative pro-oxidative multi-modal modality. We discussed possible combinations of pro-oxidative approaches with existing therapeutics in oncology prior to the forecast of future research directions. This paper identified the fundamental mechanics driving metastasis organotropism and proposed intervention strategies accordingly. Insights provided here may offer clues for the design of innovative solutions that may open a new paradigm for cancer treatment.
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spelling doaj-art-66100d387fa84a09b3da8dba96d4feea2025-08-20T02:11:58ZengSpringerMolecular Biomedicine2662-86512025-04-016113010.1186/s43556-025-00261-yCancer metastasis: molecular mechanisms and therapeutic interventionsXiaofeng Dai0Ming Xi1Jitian Li2National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong UniversityNational Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong UniversityMolecular Biology Lab, Henan Luoyang Orthopedic Hospital (Henan Provincial Orthopedic Hospital)Abstract The metastatic cascade is a complicated process where cancer cells travel across multiple organs distant from their primary site of onset. Despite the wide acceptance of the ‘seed and soil’ theory, mechanisms driving metastasis organotropism remain mystery. Using breast cancer of different subtypes as the disease model, we characterized the ‘metastatic profile of cancer cells’ and the ‘redox status of the organ microenvironment’ as the primary determinants of cancer metastasis organotropism. Mechanically, we identified a positive correlation between cancer metabolic plasticity and stemness, and proposed oxidative stress as the selection power of cancer cells succeeding the metastasis cascade. Therapeutically, we proposed the use of pro-oxidative therapeutics in ablating cancer cells taking advantages of this fragile moment during metastasis. We comprehensively reviewed current pro-oxidative strategies for treating cancers that cover the first line chemo- and radio-therapies, approaches relying on naturally existing power including magnetic field, electric field, light and sound, nanoparticle-based anti-cancer composites obtained through artificial design, as well as cold atmospheric plasma as an innovative pro-oxidative multi-modal modality. We discussed possible combinations of pro-oxidative approaches with existing therapeutics in oncology prior to the forecast of future research directions. This paper identified the fundamental mechanics driving metastasis organotropism and proposed intervention strategies accordingly. Insights provided here may offer clues for the design of innovative solutions that may open a new paradigm for cancer treatment.https://doi.org/10.1186/s43556-025-00261-yCancerMetastasis organotropismOnco-therapeuticsOxidative stressMetabolismCold atmospheric plasma
spellingShingle Xiaofeng Dai
Ming Xi
Jitian Li
Cancer metastasis: molecular mechanisms and therapeutic interventions
Molecular Biomedicine
Cancer
Metastasis organotropism
Onco-therapeutics
Oxidative stress
Metabolism
Cold atmospheric plasma
title Cancer metastasis: molecular mechanisms and therapeutic interventions
title_full Cancer metastasis: molecular mechanisms and therapeutic interventions
title_fullStr Cancer metastasis: molecular mechanisms and therapeutic interventions
title_full_unstemmed Cancer metastasis: molecular mechanisms and therapeutic interventions
title_short Cancer metastasis: molecular mechanisms and therapeutic interventions
title_sort cancer metastasis molecular mechanisms and therapeutic interventions
topic Cancer
Metastasis organotropism
Onco-therapeutics
Oxidative stress
Metabolism
Cold atmospheric plasma
url https://doi.org/10.1186/s43556-025-00261-y
work_keys_str_mv AT xiaofengdai cancermetastasismolecularmechanismsandtherapeuticinterventions
AT mingxi cancermetastasismolecularmechanismsandtherapeuticinterventions
AT jitianli cancermetastasismolecularmechanismsandtherapeuticinterventions