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Molecularly Targeted Therapy and Immunotherapy: The Next Frontier in Metastatic Bladder Cancer

Arjun Vasant Balar, MD
Published: Wednesday, Aug 27, 2014
NYU Cancer InstituteArjun Vasant Balar, MD
Arjun Vasant Balar, MD
Assistant Professor, Department of Medicine
Co-Leader, Genitourinary Cancers Program
Laura and Isaac Perlmutter Cancer Center
at NYU Langone Medical CenterDr. Yixuan Gong
The last major breakthrough in treatment for metastatic bladder (urothelial) cancer occurred in the 1980s, when cisplatin-based therapies, specifically MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin), became the new standard of care. A major step toward improved tolerability of cisplatin-based therapy came in the early 2000s with the advent of the modern regimen of gemcitabine and cisplatin. However, the number of individuals who respond to this type of chemotherapy and the average survival have not significantly changed. More effective and better tolerated treatments remain a critical need.

Recent efforts toward the comprehensive molecular characterization of muscle-invasive urothelial bladder cancer—notably, the recent publication by The Cancer Genome Atlas (TCGA) Research Network in the journal Nature (2014;507[7492]:315-322)—have provided a detailed landscape of the varied genetic alterations in muscle-invasive urothelial cancer, giving promise to future trials of targeted therapies that may be selectively used to treat a specific patient’s tumor. With novel molecular biology dramatically opening up the field, intensified research is pointing to the identification of genetic biomarkers and better tolerated and more effective molecularly targeted therapies.

Immunomodulatory agents are also a new and promising class of treatments that present newfound optimism for the treatment of bladder cancer. First tested in patients with advanced melanoma, this class of immune-targeted therapy—more specifically, “immune checkpoint inhibitors”—also has the potential to revolutionize the treatment of advanced non– small cell lung cancer and advanced renal cell cancer, and is now being tested in advanced bladder cancer.

Bladder cancer researchers at NYU Langone Medical Center and its Laura and Isaac Perlmutter Cancer Center are working to better understand the mechanisms underlying the anticancer effect of these therapies, with the intent to help design the optimal treatment strategy for an individual patient.

As molecularly targeted therapies and immunetargeted therapies move through clinical trials, we hope to make major strides in improving the lives of patients with this devastating disease.

Immune Checkpoint Inhibitors

In June, recruitment commenced at NYU Langone and several clinical centers across the country on a multicenter, phase II, single-arm study of the immune checkpoint inhibitor MPDL3280A for advanced bladder cancer. This promising agent is a monoclonal antibody that blocks PD-L1, which is commonly expressed on bladder cancer cells, from binding to one of its receptors, PD-1, which is expressed on specific anticancer T cells. When activated, the PD-1 receptor on T cells signals an “off-switch” or “checkpoint” for these T cells, preventing its anticancer effect and allowing the bladder cancer cells to grow and invade unchecked. By blocking this interaction, we hope to reactivate the body’s own immune system against bladder cancer.

A particular strength of NYU Langone’s Perlmutter Cancer Center is the research of our dedicated laboratory, led by Xue-Ru Wu, MD, professor of Urology and Pathology, in studying bladder cancer biology in a mouse model of bladder cancer with an intact immune system.

His work using transgenic mouse models of bladder cancer has led to seminal insights into the molecular biology of bladder cancer and now serves as a unique model in which to test and better understand immune checkpoint inhibitors.


View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Clinical Interchange™: Translating Research to Inform Changing Paradigms: Assessment of Emerging Immuno-Oncology Strategies and Combinations across Lung, Head and Neck, and Bladder CancersOct 31, 20182.0
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