Integrating basic science and clinical research in bladder cancer: update from the first bladder Specialized Program of Research Excellence (SPORE).

Abstract

To review the progress of the genitourinary SPORE (Specialized Program of Research Excellence) in bladder cancer. The optimal management of bladder cancer depends on the accurate assessment of the biological potential of the disease. Methotrexate, vincristine, adriamycin and cisplatin (M-VAC) chemotherapy has been the standard of therapy for over a decade. However, there has been no improvement in patient survival. Encouraging preclinical data have resulted in the rapid translation of epidermal growth factor receptor antagonists into the clinic. However, phase I and II single-agent clinical trials in head and neck, lung, and colon cancer failed to match the hope generated by laboratory investigations since only a minority of patients seemed to benefit from this approach. Nonetheless, recent data revealed that non-small-cell lung cancer tumors that responded to single-agent Iressa possessed activating epidermal growth factor receptor mutations. These findings have generated refound interest for epidermal growth factor receptor-dependent tumors that are identified by molecular and pharmacodynamic approaches prior to or early in the course of therapy. Targeted therapy against epidermal growth factor receptor has become one of the primary focuses of the genitourinary SPORE in bladder cancer. The SPORE grant scheme is designed to encourage rapid development of new and innovative cancer research in areas of high priority, in this case bladder cancer. The SPORE has facilitated the advancement of novel epidermal growth factor receptor-targeted therapy, such as the monoclonal antibody IMC-225 and the tyrosine kinase inhibitor ZD1839 (Iressa), from the laboratory to clinical trials. The integration of these new biological agents in combination with chemotherapy, in order to abrogate the progression of advanced bladder cancer, is the prime directive of our current phase II Iressa/docetaxel trial.