In vitro and in vivo effects of the PPAR-alpha agonists fenofibrate and retinoic acid in endometrial cancer

The combination of fenofibrate and retinoic acid is a potent inhibitor of Ishikawa endometrial cancer cell growth in vitro.Endometrial cancer is the most prevalent gynaecological cancer in the UK, and represents the third commonest cancer affecting women in the Western World [1]. By contrast, the incidence in the non-Western world is approximately ten-fold lower [2]. The excellent prognosis of early stage endometrial cancers belies the impact of the disease on mortality, being of similar magnitude to that of cervical cancer [2]. Indeed, the long-term survival of advanced stage endometrial cancer, at approximately 10%, is similar to that of ovarian cancer.Established risk factors for sporadic endometrial cancer mainly involve hormonal factors, with the unopposed estrogen hypothesis believed to be the central pathogenetic mechanism [3,4]. Although this theory is strongly supported, it does not satisfactorily account for all the risk factors associated with endometrial cancer risk. Obesity is a significant independent risk factor, with relative risks in the 2–10 range [5,6]. The mechanism for this has not yet been elucidated but postulates include the collateral involvement of estrogen and insulin-like growth factor (IGF) receptor pathways [5,7]. Improving understanding of the carcinogenesis of endometrial cancer is essential in the development of targeted therapy.The potential of gene array methods and systems biology has been exploited in recent years for the investigation of a number of tumour types [8,9]. The aim of the new biology is to provide a global overview of carcinoma at the molecular level, whilst focusing on biologically relevant data. Although oncology has received a great deal of attention from computational biology, a limited number of gene array studies have been applied solely to endometrial cancer [10-12].Using gene array methods within a computational biology environment, we have previously demonstrated that lipid metabolism is likely to play an im