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Repurposing Drugs in Oncology (ReDO)-diclofenac as an anti-cancer agent
Pan Pantziarka1, Vidula Sukhatme2, Gauthier Bouche3
1Anticancer Fund, Brussels, 1853 Strombeek-Bever, Belgium; The George Pantziarka TP53 Trust, London, UK.
Abstract:
Diclofenac (DCF) is a well-known and widely used non-steroidal anti-inflammatory drug (NSAID), with a range of actions which are of interest in an oncological context. While there has long been an interest in the use of NSAIDs in chemoprevention, there is now emerging evidence that such drugs may have activity in a treatment setting. DCF, which is a potent inhibitor of COX-2 and prostaglandin E2 synthesis, displays a range of effects on the immune system, the angiogenic cascade, chemo- and radio-sensitivity and tumour metabolism. Both pre-clinical and clinical evidence of these effects, in multiple cancer types, is assessed and summarised and relevant mechanisms of action outlined. Based on this evidence the case is made for further clinical investigation of the anticancer effects of DCF, particularly in combination with other agents - with a range of possible multi-drug and multi-modality combinations outlined in the supplementary materials accompanying the main paper.
Insights
Diclofenac (DCF), a non-steroidal anti-inflammatory drug, shows promise as an anticancer treatment. Research suggests DCF impacts tumor metabolism, immune response, and sensitivity to chemotherapy and radiation, warranting further clinical investigation.
Area of Science:
- Oncology
- Pharmacology
- Immunology
Background:
- Non-steroidal anti-inflammatory drugs (NSAIDs) like Diclofenac (DCF) are recognized for their anti-inflammatory properties.
- Emerging evidence suggests NSAIDs may possess therapeutic activity in cancer treatment, beyond chemoprevention.
Purpose of the Study:
- To assess pre-clinical and clinical evidence of Diclofenac's anticancer effects across various cancer types.
- To outline the mechanisms of action through which DCF may exert its anti-cancer effects.
- To advocate for further clinical trials investigating DCF, particularly in combination therapies.
Main Methods:
- Review and summary of existing pre-clinical and clinical data on Diclofenac in oncology.
- Analysis of Diclofenac's impact on key cancer-related pathways, including COX-2 inhibition, prostaglandin E2 synthesis, immune modulation, angiogenesis, and tumor metabolism.
- Identification of potential combination strategies with other anti-cancer agents and modalities.
Main Results:
- Diclofenac demonstrates effects on the immune system, angiogenic cascade, and tumor metabolism.
- Evidence suggests Diclofenac can influence chemo- and radio-sensitivity.
- Pre-clinical and clinical data support Diclofenac's potential anti-cancer activity in multiple tumor types.
Conclusions:
- Diclofenac exhibits multiple mechanisms relevant to cancer treatment.
- Further clinical investigation of Diclofenac's anti-cancer effects is warranted.
- Combination therapies involving Diclofenac may offer enhanced therapeutic benefits.
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