Leukotriene Signaling in Cancer Progression
Summary
Leukotrienes are bioactive lipid mediators derived from the 5-lipoxygenase pathway of arachidonic acid metabolism. In cancer, both leukotriene B4 (LTB4) and the cysteinyl leukotrienes (LTC4, LTD4, LTE4) contribute to tumour initiation, progression and metastasis through multiple mechanisms. These include direct stimulation of cancer cell proliferation and survival, modulation of angiogenesis and remodelling of the extracellular matrix, and crosstalk with immune and stromal cells within the tumour microenvironment. Overexpression of 5-lipoxygenase (5-LOX) and upregulation of cysteinyl leukotriene receptors (CysLT1R, CysLT2R) have been documented in a range of solid and haematological malignancies, correlating with poor prognosis and chemoresistance. Emerging evidence also points to non-canonical, lipid-mediator-independent functions of 5-LOX in regulating gene expression and miRNA processing, further broadening the impact of leukotriene signalling on tumour biology and therapeutic response.
Research from Nature Portfolio
Recent studies have shown that long-term use of cysteinyl leukotriene receptor antagonists in patients with chronic inflammatory airway disease is associated with a marked reduction in cancer incidence in a dose-dependent manner. A large-scale pharmacoepidemiological investigation demonstrated that antagonism of CysLT1R not only lowers the risk of new-onset malignancies but also provides insights into repurposing these well-tolerated agents for chemoprevention. The findings have spurred interest in clinical trials exploring montelukast and related drugs as adjuncts to standard oncological therapies.
Leukotriene Signaling in Cancer Progression publication trend
The graph below shows the total number of articles in leukotriene signaling in cancer progression across all publications each year (not limited to Nature Index journals).
Technical terms
Leukotrienes: Lipid mediators produced by 5-lipoxygenase that regulate inflammation and modulate cancer cell behaviour.
5-Lipoxygenase (5-LOX): The key enzyme catalysing the conversion of arachidonic acid into leukotriene precursors.
Cysteinyl leukotriene receptors (CysLT1R, CysLT2R): G-protein-coupled receptors that bind LTC4, LTD4 and LTE4, initiating pro-tumourigenic signalling cascades.
Tumour-associated macrophages (TAMs): Macrophage populations within the tumour microenvironment that can adopt a pro-inflammatory or immunosuppressive phenotype, influenced by leukotriene signalling.
Non-canonical functions: Roles of 5-LOX beyond lipid mediator synthesis, including modulation of gene transcription and miRNA processing.
References
- Cross-Talk between Cancer Cells and the Tumour Microenvironment: The Role of the 5-Lipoxygenase Pathway. International Journal of Molecular Sciences (2017).
- The role of human 5-Lipoxygenase (5-LO) in carcinogenesis - a question of canonical and non-canonical functions. Oncogene (2024).
- Hepatocellular carcinoma progression promoted by 5-lipoxygenase activity in CD163(+) tumor-associated macrophages. Biomedicine & Pharmacotherapy (2023).
- Potential of Anti-Leukotriene Drugs as New Therapeutic Agents for Inhibiting Cholangiocarcinoma Progression. Molecules (2024).
- Cysteinyl Leukotriene Receptor Antagonists Decrease Cancer Risk in Asthma Patients. Scientific Reports (2016).
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