This can provide the structural basis for identifying small molecule DD1 mimetics that would be useful in targeting DIF 1 in breast and prostate cancer in animal models and in future clinical trials. Background Kidney cancer accounts for approximately 2% of all adult cancers. It is the 7th leading cause of http://www.selleckchem.com/products/Gemcitabine-Hydrochloride(Gemzar).html cancer in the US with an estimated incidence of approximately 51,000 new can cer cases per year in 2007. Renal cell carcinoma is the most common tumour arising from the cells in the lining of tubules in the kidney. At the time of diagno sis, 30% of patients will have metastatic or unresectable disease, and the 2 year overall survival of this cohort is 10%. The incidence of kidney cancer is rising. it is 2 times more common in men than women. Risk factors include obesity, smoking and hypertension.

RCC is a chemoresistant tumour usually exhibiting only a marginal response. Radiotherapy and chemotherapy are generally ineffective in the treatment of advanced renal tumours. The intrinsic occurrence of multidrug resistance modulates the Inhibitors,Modulators,Libraries resistance of tumours to a wide variety of and structurally distinct chemotherapeu tic drugs through the expression of drug efflux pumps. Two of the most widely studied efflux pumps, MDR 1 P gp P 170, the gene product of MDR 1 and MRP 1 which encodes a 190 kDa membrane protein have both been demonstrated to pump a wide variety of the most commonly used cancer drugs out of tumour cells. Their over expression correlates broadly with drug resistance in many different forms of cancer including pancreatic cancer, lung cancer, breast cancer and glioma.

The relative contributions and causative role, if any, of MDR associated protein efflux pumps Inhibitors,Modulators,Libraries in Inhibitors,Modulators,Libraries renal carcinoma have not been fully elucidated. Studies detailing the prevalence and contribution of MDR 1 P gp in RCC are conflicting. MDR 1 P gp expres sion has been reported widely in untreated renal carcino mas. It does appear that intrinsic drug resistance exists in many renal RCC and it is associated, at least in part, with increased expression of MDR 1 P gp. However, the exact prognostic significance of this expression remains unclear with conflicting results described. Longer progression free survival has been observed in patients with none or very few MDR 1 P gp positive tumour cells compared to patients with a larger proportion of MDR 1 Pgp positive tumour cells, however higher MDR 1 expression has Inhibitors,Modulators,Libraries been associated with a better outcome also.

Expression of MDR 1 P gp has been shown to correlate with a well Inhibitors,Modulators,Libraries differentiated tumour phenotype in renal carcinoma. Higher MDR 1 gene expres sion has been observed in RCCs that have metastasised invaded through the renal capsule compared to early stage non invasive tumours. Studies addressing the contribution, if any, of the MRP 1 efflux pump and its any other enquiries gene product in this disease are lim ited.