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REVIEW ARTICLE

Cancer as a syntrophic cellular consortium established by fatty acid oxidation–primed mitochondria and carrier macrophages

Abhijit Deonath1*
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1 Department of Agriculture, Fisheries and Forestry, Australian Government, Canberra , Australia
GPD, 026280024 https://doi.org/10.36922/GPD026280024
Received: 12 July 2026 | Revised: 25 September 2026 | Accepted: 29 September 2026 | Published online: 27 October 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

The escalating clinical link between cardiovascular disease and subsequent cancer suggests a systemic etiology beyond the sole purview of somatic mutation. This article reviews emerging evidence through a novel lens: cancer as a syntrophic cellular consortium, where metabolic stratification, driven by fatty acid oxidation (FAO)-primed mitochondria and mediated by carrier macrophages, establishes functionally distinct, metabolically interdependent cellular subpopulations. Stressed cardiomyocytes eject metabolically “primed” mitochondria. These organelles are engulfed by macrophages, transforming them into pathogenic “mito-macrophages” that act as mobile systemic carriers. These mito-macrophages instigate malignancy through mitochondrial transfer to recipient cells, inducing profound metabolic and epigenetic reprogramming. Within individual cells, the transferred mitochondria establish distinct intracellular oxidation zones fueled by FAO, juxtaposed with hypoxia zones favoring glycolysis. This primary compartmentalization scales up within the evolving tumor: cells from oxidation zones adopt a “leader” phenotype, characterized by high FAO, metabolic flexibility, and invasive capacity, while cells from hypoxia zones become “follower” phenotypes, relying on glycolysis and contributing to bulk tumor growth. Critical intercellular signaling pathways between these emerging “leader” and “follower” populations are central to establishing, maintaining, and propagating this obligate, syntrophic cross-feeding hierarchy, ensuring tumor progression. This framework bridges cardiac stress and distal cancer, elucidating how metabolic and epigenetic imprinting dictates cellular roles within a structured malignant consortium. Reconceiving cancer as such a syntrophic system offers new avenues for therapeutic intervention, targeting metabolic instigators and the signaling axes that define its consortium partners. This framework synthesizes established biological mechanisms into a novel, testable hypothesis and is presented as such. Direct experimental evidence for several of the proposed linkages—particularly long-distance macrophage-mediated trafficking of cardiomyocyte-derived mitochondria, and the FAO-primed state—remains to be established.

Graphical abstract
Keywords
Cancer
Mitochondria
Fatty acid oxidation
Cardiomyocytes
Macrophages
Syntrophy
Funding
None.
Conflict of interest
The author declares no competing interests in relation to the publication of this paper.
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Gene & Protein in Disease, Electronic ISSN: 2811-003X Published by AccScience Publishing
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