Cancer biology & therapy · 2026
The dual role of leukotrienes in the tumor microenvironment: balancing pro-tumorigenic and anti-tumor immunity.
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Thake Andrew, Caruso Maria, Fernandez-Bussy Sebastian, Sacco Keith
Аннотация
BACKGROUND: Leukotrienes are bioactive lipid mediators produced via the 5-lipoxygenase (5-LO) pathway and are essential for inflammatory signaling in the tumor microenvironment (TME), playing roles in angiogenesis, immune modulation and metastatic progression.
OBJECTIVE: This review evaluates the role of leukotriene signaling in cancer progression and highlights biomarker-guided therapeutic strategies targeting these pathways in the TME.
METHODS: A narrative review of preclinical, clinical, and epidemiological studies was performed, with prespecified inclusion criteria and prioritization of recent evidence.
RESULTS: Leukotriene-mediated signaling correlates with biomarkers such as CysLT1 receptor expression, β-catenin activation, and HIF-1α signaling. In preclinical models, pharmacological agents including montelukast, zileuton, and FLAP antagonists suppress tumor growth, and restore apoptotic signaling; current clinical evidence remains largely observational and pharmacoepidemiologic.
CONCLUSION: Targeting this pathway represents a promising avenue in oncology, with potential to enhance precision medicine through biomarker-guided patient stratification. Further clinical validation is warranted to translate these findings into therapeutic benefit.
OBJECTIVE: This review evaluates the role of leukotriene signaling in cancer progression and highlights biomarker-guided therapeutic strategies targeting these pathways in the TME.
METHODS: A narrative review of preclinical, clinical, and epidemiological studies was performed, with prespecified inclusion criteria and prioritization of recent evidence.
RESULTS: Leukotriene-mediated signaling correlates with biomarkers such as CysLT1 receptor expression, β-catenin activation, and HIF-1α signaling. In preclinical models, pharmacological agents including montelukast, zileuton, and FLAP antagonists suppress tumor growth, and restore apoptotic signaling; current clinical evidence remains largely observational and pharmacoepidemiologic.
CONCLUSION: Targeting this pathway represents a promising avenue in oncology, with potential to enhance precision medicine through biomarker-guided patient stratification. Further clinical validation is warranted to translate these findings into therapeutic benefit.