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Eicosanoids in Cancer: New Roles in Immunoregulation
Amber M Johnson1, Emily K Kleczko1, Raphael A Nemenoff1
1Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Frontiers in Pharmacology
|December 28, 2020
Summary
Eicosanoids, lipid mediators derived from arachidonic acid, play a role in cancer. Targeting these pathways, including prostaglandin E2, offers potential for combination therapies with immune checkpoint inhibitors.
Area of Science:
- Biochemistry
- Immunology
- Oncology
Background:
- Eicosanoids are bioactive lipids derived from arachidonic acid via COX, 5-LO, and cytochrome P450 pathways.
- Increased eicosanoid production is linked to inflammation and cancer, with prostaglandin E2 (PGE2) promoting tumor growth.
- While COX-2 inhibitors showed promise, toxicity limited their use; immunotherapy has advanced cancer treatment, but response rates vary.
Purpose of the Study:
- To review the role of eicosanoids in cancer.
- To focus on eicosanoid modulation of the tumor microenvironment and anti-tumor immunity.
- To explore other eicosanoids beyond PGE2 in cancer progression and immune evasion.
Main Methods:
- Literature review of eicosanoid pathways in cancer.
- Analysis of the role of prostaglandin E2 (PGE2) in tumor proliferation and metastasis.
- Examination of lipoxygenase and cytochrome P450 pathway products in modulating the tumor microenvironment.
Main Results:
- Prostaglandin E2 (PGE2), produced by COX-2, drives cancer cell proliferation and metastasis.
- PGE2 exhibits immunosuppressive activity, impacting anti-tumor immunity.
- Other eicosanoids from lipoxygenase and cytochrome P450 pathways also influence the tumor microenvironment.
Conclusions:
- Eicosanoids are key regulators of the tumor microenvironment and immune response in cancer.
- Targeting eicosanoid pathways, including PGE2 and others, is a promising strategy for combination therapy.
- Small molecule inhibitors and receptor blockers offer potential for novel cancer therapeutics, especially with immune checkpoint inhibitors.
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