Columbia-Presbyterian Cancer Center
New York City, NY

T.J. Martell Annual Summary

Columbia University Medical Center
Principal Investigator: Mitchell C Benson, M.D.

Co-Investigators: I. Bernard Weinstein, M.D., Ph.D.
Carlos Cordon-Cardo, M.D., Ph.D.
Ralph Buttyan, Ph.D.
Daniel Petrylak, M.D.

The research group at Columbia University has made great advances over the past year. We added a new senior faculty member to our research team, Carlos Cordon-Cardo, M.D., Ph.D. Dr. Cordon-Cardo moved to Columbia from Memorial Sloan- Kettering Cancer Center (MSKCC) in August, 2006. At MSKCC, he had served as the Director of the Urology Tumor and Serum Bank and was a leader in the Urology Research program. He is a world leader and a pioneer in systems pathology.

Over the past year, we have made important steps towards our goal of controlling and curing prostate cancer. We expanded our understanding of the mechanism of anti-male hormone therapy in human prostate cancer. We have demonstrated that when male hormones are removed from a patient with prostate cancer, the first effect is on the vascular integrity of the prostate cancer. We are developing a clinical trial to couple anti-vascular drugs with anti-male hormone therapies to potentiate the effects of these two strategies. Currently, virtually every man with advanced prostate cancer will be treated with anti-male hormone therapies at some time during his life. The enhancement of theses treatments is of great potential importance and will have a huge impact on this treatment strategy.

During 2006, we further defined the role of ProtoCadherin-PC, the gene discovered in our laboratories, in the evolution of hormone refractory prostate cancer (the type of prostate cancer that can lead to death) and we anticipate the beginning of human trials aimed at controlling this unique gene over the coming year. ProtoCadherin-PC is a gene that allows prostate cancers to grow after anti-male hormone therapies stop working. If this can be blocked, patients with advanced prostate cancer could be placed into very durable remissions.

Although our work on the vascular effects of anti-male hormone therapy and on ProtoCadherin-PC are both currently funded by the National Cancer Institute, the pioneering work was made possible by the support of the T.J. Martell Foundation and without that support, these breakthroughs would definitely have been delayed and might not have occurred.

Dr. Carlos Cordon-Cardo is an expert in systems based pathology and his addition to our team complements our research very well. Prostate cancer is a complex, heterogeneous disease with a natural history that evokes considerable debate with respect to appropriate treatment options, especially for localized disease. Dr. Carlos Cordon-Cardo has developed a systems pathology approach for interrogating prostate cancer which is unique in that it integrates clinical variables with histological features, and quantitative molecular profiles derived from biomarker analyses. The method for building predictive personalized models is achieved through the application of novel technologies in the areas of object-oriented image analysis, pattern recognition, and biomarker multiplexing with spectral microscopic imaging. The obtained complex datasets are analyzed with machine learning analytics that render probabilities for a particular clinical outcome or event. He has applied this approach on prostatectomy specimens and has been able to create a test for predicting a patients’ likelihood of PSA recurrence as well as progressive disease.

“Systems Pathology” represents a turning point in the practice of pathology. By combining the clinical history with the various quantitative and molecular attributes of a given diagnostic specimen, we believe we are now able to develop more accurate personalized predictive models which ideally will impact on treatment decisions and therapeutic options.

All of us at Columbia University are grateful to the T.J. Martell Foundation for its ongoing support of our research and wish to thank all of you for your financial support and the confidence you show in us by that support.