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Integrating basic science and clinical research in bladder cancer: update from the first bladder Specialized Program
Ralph A Highshaw1, David J McConkey, Colin P Dinney
1Department of Urology and Cancer Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. rhighshaw@mdanderson.org
Purpose Of Review:
To review the progress of the genitourinary SPORE (Specialized Program of Research Excellence) in bladder cancer.
Recent Findings:
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.
Summary:
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.
Insights
The genitourinary SPORE program is advancing bladder cancer research by focusing on targeted therapies. New treatments targeting epidermal growth factor receptor show promise for improving patient outcomes.
Area of Science:
- Oncology
- Genitourinary Cancer Research
- Molecular Targeted Therapy
Background:
- Bladder cancer management requires accurate assessment of disease potential.
- Methotrexate, vincristine, adriamycin, and cisplatin (M-VAC) chemotherapy has been standard but offers no survival improvement.
- Epidermal growth factor receptor (EGFR) antagonists show promise but require patient selection.
Purpose of the Study:
- To review the progress of the genitourinary Specialized Program of Research Excellence (SPORE) in bladder cancer.
- To highlight the development of novel EGFR-targeted therapies.
Main Methods:
- Review of preclinical and clinical trial data for EGFR antagonists.
- Focus on molecular and pharmacodynamic approaches for patient identification.
- Integration of targeted therapy with chemotherapy in clinical trials.
Main Results:
- Preclinical data support EGFR antagonists, but early clinical trials showed limited benefit.
- Activating EGFR mutations identified in responders to single-agent Iressa (ZD1839).
- Refound interest in EGFR-dependent tumors identified by molecular approaches.
Conclusions:
- EGFR-targeted therapy is a primary focus of the genitourinary SPORE for bladder cancer.
- SPORE facilitates advancement of therapies like IMC-225 and ZD1839 (Iressa) to clinical trials.
- Current research integrates targeted agents with chemotherapy to combat advanced bladder cancer.
