Specialized pro-resolving mediators and cancer: news and promises from the other side of the moon
- 1Department of Medicine, Laboratory of Molecular Medicine and Biotechnology, Campus Bio Medico University of Rome , ,
Abstract
In physiological settings, inflammation is not passively terminated but actively resolved through coordinated endogenous programs. A central component of this response is the biosynthesis of specialized pro-resolving mediators (SPMs), including lipoxins, resolvins, protectins, and maresins. These SPMs arise from polyunsaturated fatty acid precursors that are partially shared with those of classical pro-inflammatory mediators, such as prostaglandins and leukotrienes. Rather than broadly suppressing immunity, SPMs promote the restoration of tissue homeostasis by limiting excessive leukocyte recruitment, enhancing efferocytosis, and reprogramming inflammatory responses. Inflammation is a recognized enabler of cancer, contributing to the main hallmarks of tumor progression, such as sustained proliferative signaling, angiogenesis, and immune evasion. A chronically inflamed tumor microenvironment fosters cancer progression in a complex, tumor- and stage-specific manner. This persistent inflammatory context has supported the prescient view of tumors as “wounds that do not heal.” While the pro-tumorigenic functions of inflammatory lipid mediators, such as prostaglandin E ₂ , are well established, the contribution of defective resolution programs to cancer progression remains less clear. This review examines the lipid mediator networks linking the initiation and resolution of inflammation in solid tumors, focusing on the mechanistic roles of SPMs in the tumor microenvironment and the emerging translational opportunities to restore pro-resolving signaling. This supports a re-evaluation of cancer-associated inflammation from the perspective of failed resolution, opening avenues for therapeutic strategies targeting resolution to mitigate therapy resistance. We develop this idea by bringing together direct and indirect scientific evidence, explicitly distinguished throughout the text and summarized in a dedicated evidence table, and by focusing on a prospective pharmacological scenario. This is a narrative review; its scope, literature search strategy, and limitations are described in Sections 1.1, 1.2, and 8.
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BibTeX
@article{gatti2026specialized,
title = {{Specialized pro-resolving mediators and cancer: news and promises from the other side of the moon}},
author = {V. Gatti and G. Colella and F. Violante and V. M. Fazio and M. Cioce},
journal = {Frontiers in pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1907377},
url = {https://europepmc.org/article/PMC/PMC13669855},
note = {CC BY},
}
RIS
TY - JOUR
TI - Specialized pro-resolving mediators and cancer: news and promises from the other side of the moon
AU - V. Gatti
AU - G. Colella
AU - F. Violante
AU - V. M. Fazio
AU - M. Cioce
PY - 2026
DA - 2026/10/01
JO - Frontiers in pharmacology
DO - 10.3389/fphar.2026.1907377
UR - https://europepmc.org/article/PMC/PMC13669855
AB - In physiological settings, inflammation is not passively terminated but actively resolved through coordinated endogenous programs. A central component of this response is the biosynthesis of specialized pro-resolving mediators (SPMs), including lipoxins, resolvins, protectins, and maresins. These SPMs arise from polyunsaturated fatty acid precursors that are partially shared with those of classical pro-inflammatory mediators, such as prostaglandins and leukotrienes. Rather than broadly suppressing immunity, SPMs promote the restoration of tissue homeostasis by limiting excessive leukocyte recruitment, enhancing efferocytosis, and reprogramming inflammatory responses. Inflammation is a recognized enabler of cancer, contributing to the main hallmarks of tumor progression, such as sustained proliferative signaling, angiogenesis, and immune evasion. A chronically inflamed tumor microenvironment fosters cancer progression in a complex, tumor- and stage-specific manner. This persistent inflammatory context has supported the prescient view of tumors as “wounds that do not heal.” While the pro-tumorigenic functions of inflammatory lipid mediators, such as prostaglandin E ₂ , are well established, the contribution of defective resolution programs to cancer progression remains less clear. This review examines the lipid mediator networks linking the initiation and resolution of inflammation in solid tumors, focusing on the mechanistic roles of SPMs in the tumor microenvironment and the emerging translational opportunities to restore pro-resolving signaling. This supports a re-evaluation of cancer-associated inflammation from the perspective of failed resolution, opening avenues for therapeutic strategies targeting resolution to mitigate therapy resistance. We develop this idea by bringing together direct and indirect scientific evidence, explicitly distinguished throughout the text and summarized in a dedicated evidence table, and by focusing on a prospective pharmacological scenario. This is a narrative review; its scope, literature search strategy, and limitations are described in Sections 1.1, 1.2, and 8.
SN - 1663-9812
ER -