PROSTAGLANDINS AND CANCER (original) (raw)

Recent advances in basic science

PROSTAGLANDINS AND CANCER

D Wang1,
R N DuBois2
1Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
2Departments of Medicine, Cancer Biology, and Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN, USA, and The Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
Correspondence to:
Professor R N DuBois
The Vanderbilt-Ingram Cancer Center, Room 698, Preston Research Building, 2300 Pierce Ave, Nashville, Tennessee 37232-6838, USA; raymond.dubois@vanderbilt.edu

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SUMMARY

Chemoprevention has been considered as a possible approach for cancer prevention. A significant effort has been made in the development of novel drugs for both cancer prevention and treatment over the past decade. Recent epidemiological studies and clinical trials indicate that long term use of aspirin and similar agents, also called non-steroidal anti-inflammatory drugs (NSAIDs), can decrease the incidence of certain malignancies, including colorectal, oesophageal, breast, lung, and bladder cancers. The best known targets of NSAIDs are cyclooxygenase (COX) enzymes, which convert arachidonic acid to prostaglandins (PGs) and thromboxane. COX-2 derived prostaglandin E2(PGE2) can promote tumour growth by binding its receptors and activating signalling pathways which control cell proliferation, migration, apoptosis, and/or angiogenesis. However, the prolonged use of high dosages of COX-2 selective inhibitors (COXIBs) is associated with unacceptable cardiovascular side effects. Thus it is crucial to develop more effective chemopreventive agents with minimal toxicity. Recent efforts to identify the molecular mechanisms by which PGE2 promotes tumour growth and metastasis may provide opportunities for the development of safer strategies for cancer prevention and treatment.

INTRODUCTION

The most effective treatments for cancer, including various combinations of surgical resection, radiation, and/or chemotherapy, depend on the detection of cancer at a very early stage. Unfortunately, it has not been possible to identify all individuals who are at the highest risk for developing cancer. Most patients present to their physician with advanced cancer when standard treatment regimens for solid malignancies result in a much lower five year survival. It is generally agreed that an effective way to control cancer is to find better ways of preventing it. Chemopreventive approaches are definitely worth considering for healthy persons who have a strong family history of cancer or those who are particularly susceptible for other reasons. One promising group of compounds with cancer preventive …