Cyclooxygenase-2 Inhibition in Cancer Therapeutics

Cyclooxygenase-2 (COX-2) is an inducible enzyme that catalyses the conversion of arachidonic acid into prostanoids, notably prostaglandin E2 (PGE2), which orchestrates inflammatory signalling within tumours. Aberrant COX-2 expression is a hallmark of many solid malignancies, driving angiogenesis, proliferation, invasiveness and escape from immune surveillance. Inhibition of COX-2 by non-steroidal anti-inflammatory drugs (NSAIDs) or selective COX-2 antagonists has been shown to impair tumour growth in preclinical models and to reduce cancer incidence and mortality in population studies. Mechanistically, COX-2 blockade disrupts PGE2-mediated suppression of dendritic cells, T cells and natural killer cells, and limits repopulation of residual cancer stem cells after chemotherapy or radiotherapy. Aspirin, an irreversible COX-1 inhibitor with secondary COX-2 activity, is under evaluation as an adjuvant to prevent metastasis and recurrence. Clinical translation is balanced against cardiovascular and gastrointestinal risks, prompting the pursuit of biomarker-guided treatment, combination regimens with immune checkpoint inhibitors and the development of next-generation, tissue-selective modulators. COX-2 inhibition thus represents a globally significant strategy that bridges inflammation, immunity and tumour biology.

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Cyclooxygenase-2 Inhibition in Cancer Therapeutics publication trend

The graph below shows the total number of articles in cyclooxygenase-2 inhibition in cancer therapeutics across all publications each year (not limited to Nature Index journals).

Technical terms

Cyclooxygenase-2 (COX-2): An inducible enzyme that converts arachidonic acid to prostaglandins under inflammatory conditions, often upregulated in cancer cells.

Prostaglandin E2 (PGE2): A lipid mediator produced by COX-2 that promotes tumour growth, angiogenesis and immune suppression through EP receptors.

Non-steroidal anti-inflammatory drugs (NSAIDs): A class of medications that inhibit COX enzymes to reduce inflammation, some of which have demonstrated anticancer properties.

Tumour microenvironment: The complex milieu of cancer cells, immune infiltrates, stromal elements and signalling molecules that influences tumour progression and therapy response.

References

1. Prostaglandin E2 in the Tumor Microenvironment, a Convoluted Affair Mediated by EP Receptors 2 and 4. Pharmacological Reviews (2024).
2. Anti-Inflammatory Drugs as Anticancer Agents. International Journal of Molecular Sciences (2020).
3. Cyclooxygenase-2 promotes tumor growth and suppresses tumor immunity. Cancer Cell International (2015).
4. Cyclooxygenase‐2: A Role in Cancer Stem Cell Survival and Repopulation of Cancer Cells during Therapy. Stem Cells International (2016).
5. ADD-ASPIRIN: A phase III, double-blind, placebo controlled, randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common non-metastatic solid tumours. Contemporary Clinical Trials (2016).
6. Estimates of benefits and harms of prophylactic use of aspirin in the general population. Annals of Oncology (2014).
7. Prostaglandin E2 and Cancer: Insight into Tumor Progression and Immunity. Biology (2020).