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New investigational treatment for bladder cancer, identified with Columbia-developed research model
March 13, 2009Inhibiting the mTOR signaling pathway with a drug called rapamycin found to slow the progression of bladder tumors in mice; model demonstrates that 2 tumor suppressor genes, p53 and pten, are inactivated in invasive bladder cancer
NEW YORK - 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.
Columbia University Medical Center
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.
Columbia University Medical Center
Bladder Cancer Current Events and Bladder Cancer News RSSPrediction model superior to traditional criteria in bladder treatment decision
A statistical model can accurately predict which patients will have poor outcomes after bladder surgery and can determine the need for chemotherapy.
Hopkins scientists find cells responsible for bladder cancer's spread
Johns Hopkins scientists have tracked down a powerful set of cells in bladder tumors that seem to be primarily responsible for the cancer's growth and spread using a technique that takes advantage of similarities between tumor and organ growth.
Variation in prostate stem cell antigen gene raises bladder cancer risk
Researchers have pinpointed a specific gene variation that causes increased risk of urinary bladder cancer, according to a scientific team led by The University of Texas M. D. Anderson Cancer Center.
UT Southwestern researchers investigate high-risk populations for bladder-cancer screenings
A new study by UT Southwestern Medical Center researchers sheds light on the challenges involved in identifying which high-risk population would benefit most from bladder-cancer screening.
DKK-3 and WIF-1: Proteins related to liver cancer development?
Liver cancer is one of the most fatal human malignancies and the third most frequent cause of tumor-related death, about half a million people globally each year.
Certain ecologic factors associated with greater risk of bladder cancer
Persons drinking well water (as opposed to public supply) may be at an increased risk of bladder cancer, according to new research from the University of Alabama at Birmingham. Researchers will present data about the relationship between bladder cancer and certain ecologic factors including water source and UV radiation levels at the 104th Annual Scientific Meeting of the American Urological Association (AUA).
Mayo Clinic researcher says improved detection of bladder tumors reduces cancer recurrence
Making tumors inside the bladder fluoresce red under blue light allows physicians to more easily find and remove them, substantially reducing the rate at which these cancers come back, says a Mayo Clinic physician who is presenting results of a large, multicenter international clinical trial.
Genetic Variants Predict Recurrence of Bladder Cancer, Patient Survival
Scientists at The University of Texas M. D. Anderson Cancer Center have discovered genetic variations in the inflammation pathway that reduce the likelihood of recurrence and increase survival of patients with non-muscle invasive bladder cancer (NMIBC) who are treated with mainstream therapy.
More intense bladder cancer treatment does not improve survival, U-M study finds
Despite enduring more invasive tests and medical procedures, patients who were treated aggressively for early stage bladder cancer had no better survival than patients who were treated less aggressively.
New Discovery Raises Doubts About Use of Certain Targeted Therapies in Bladder Cancer
Researchers at the University of Virginia Health System have found that one of the genes commonly thought to promote the growth and spread of some types of cancers is in fact beneficial in bladder cancer - a major discovery that could significantly alter the way bladder cancers are treated in the future.
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