Bladder cancer caused 14,680 deaths in 2010 in the US. In advanced bladder cancer, MVAC (methotrexate, vinblastine, adriamycin and cisplatin) and GC (gemcitabine, cisplatin) combination chemotherapy demonstrate comparable efficacy with response rates of 45%- 50%. Despite the reasonable initial response to platinum based chemotherapy, median time to progression on first line therapy is only 7 months and median survival approximately 15 months. There is no standard second line therapy after platinum based chemotherapy in the US and no survival benefit has been noted with any agent. Median progression free survival (PFS) is around 2 months in platinum refractory urothelial cancer (PRUC) and overall survival (OS) is 6 - 8 months with single agent second line therapy. Combination chemotherapy does not prolong overall survival. Given the dire prognosis in PRUC and the lack of efficacy of conventional chemotherapy, preclinical investigations and clinical research have focused on identification of novel molecular targets.