Repurposing Drugs in Oncology (ReDO)-diclofenac as an anti-cancer agent.

Pan Pantziarka,Gauthier Bouche,Vidula Sukhatme,Vikas P Sukhatme,Lydie Melhuis

doi:10.3332/ecancer.2016.610

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.

Highlights

Diclofenac (DCF) is a commonly used non-steroidal anti-inflammatory drug (NSAID) used in the treatment of pain in rheumatoid arthritis and other musculoskeletal conditions, migraine, fever, acute gout and post-operative pain
This paper focuses on the evidence of an anticancer effect of DCF treatment, including data that is specific to DCF and other data that is in line with DCF’s effects as an NSAID
Analysis of high-risk neuroblastoma subsets by Larsson et al, showed that high mPGES-1 expression correlated with poor patient survival and that treatment with DCF down-regulated Prostaglandin E2 (PGE2) and that this correlated with reduced tumour growth volumes in an in vivo murine model [19]

Summary

Introduction

Diclofenac (DCF) is a commonly used non-steroidal anti-inflammatory drug (NSAID) used in the treatment of pain in rheumatoid arthritis and other musculoskeletal conditions, migraine, fever, acute gout and post-operative pain. The anti-proliferative effects of a range of NSAIDs, including DCF, were assessed in three human colon cancer cell lines (HT-29, SW480, and DLD-1) in vitro in 1994 [13].

Results

Conclusion