Inhibiting the mTOR Signaling Pathway with a Drug called Rapamycin Found to Slow the Progression of Bladder Tumors in Mice
Model Demonstrates that Two Tumor Suppressor Genes, P53 and PTEN, are Inactivated in Invasive Bladder Cancer
NEW YORK (March 12, 2009) – A team of researchers, led by Columbia University Medical Center faculty, has identified a new investigational therapy for the treatment of bladder cancer. The discovery was made using a new research model, using mice, which replicates many aspects of human bladder cancer. The model also enabled the researchers to demonstrate that two major tumor suppressor genes, p53 and PTEN, are inactivated in invasive bladder cancer. The findings and this new model are described in a paper in the March 15, 2009 issue of Genes & Development.
The new model disrupts a signaling pathway, known as mTOR, which blocks tumor growth. Inhibiting mTOR with a drug called rapamycin was found to significantly slow the progression of bladder tumors in mice.
The research was led by Drs. Cory Abate-Shen and Carlos Cordon-Cardo, both professors in the Departments of Urology and Pathology & Cell Biology and associate directors in the Herbert Irving Comprehensive Cancer Center of Columbia University Medical Center and NewYork-Presbyterian Hospital.
“We believe that this new mouse model of human bladder cancer will be invaluable to the field of bladder cancer research. Already it has provided a relevant preclinical model for therapeutic investigations and a strong rationale for targeting the mTOR signaling pathway in patients with invasive bladder cancer,” said Dr. Abate-Shen.
“Importantly, the new insights that this model has provided about the role of the inactivation of both p53 and PTEN in invasive bladder cancer may enable oncologists to more quickly identify patients with invasive disease, who may need aggressive treatment to slow the progression of their bladder cancer,” said Dr. Cordon-Cardo, who is associate director for research infrastructure at the Herbert Irving Comprehensive Cancer Center and vice-chair of pathology at Columbia University Medical Center.
Bladder cancer is a serious health problem worldwide; it is the fifth most common malignancy and a major cause of cancer morbidity and mortality. Until now, there have been few mouse models that properly replicate the invasive capabilities of this disease, leaving researchers with few tools to help them develop new therapeutic approaches for combating it.
“This new mouse model is enormously important for the study of bladder cancer,” said Daniel P. Petrylak, M.D., associate professor of medicine at Columbia University College of Physicians & Surgeons and Director of the Genitourinary Oncology Program at New York-Presbyterian Hospital/Columbia.
“Based on the initial findings about the efficacy of inhibiting the mTOR signaling pathway with rapamycin in the mouse model, I am excited to be collaborating with Dr. Abate-Shen to further investigate the implications of this research,” said James McKiernan, M.D., the John and Irene Given Associate Professor and director of urologic oncology at the Herbert Irving Comprehensive Cancer Center, who was not involved in the study.
Role of p53 and PTEN in Bladder and Other Cancers
P53 and PTEN have been found to be mutated in a significant number of advanced cancers, in bladder cancer representing approximately 41 percent of the invasive tumors and previously published research has demonstrated that their combined inactivation has profound consequences for tumor growth in many contexts, including lymphoma, prostate cancer and brain tumors. In 1997, Ramon Parsons, M.D., Ph.D., at Columbia University College of Physicians and Surgeons, led one of two teams that independently identified PTEN and discovered that knocking out PTEN sends a strong pro-growth signal on tumor cells.
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Herbert Irving Comprehensive Cancer Center
The Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center and NewYork-Presbyterian Hospital encompasses pre-clinical and clinical research, treatment, prevention and education efforts in cancer. The Cancer Center was initially funded by the NCI in 1972 and became an National Cancer Institute (NCI)-designated comprehensive cancer center in 1979. The designation recognizes the Center’s collaborative environment and expertise in harnessing translational research to bridge scientific discovery to clinical delivery, with the ultimate goal of successfully introducing novel diagnostic, therapeutic and preventive approaches to cancer. For more information, visit www.hiccc.columbia.edu.
Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia’s College of Physicians and Surgeons was the first institution in the country to grant the M.D. degree and is now among the most selective medical schools in the country. Columbia University Medical Center is home to the most comprehensive medical research enterprise in New York City and state and one of the largest in the United States. Columbia University Medical Center is affiliated with NewYork-Presbyterian Hospital, the nation’s largest not-for-profit hospital provider. For more information, please visit www.cumc.columbia.edu.