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Targeting Hypoxia in Bladder Cancer


The Brady team is investigating whether these cancers are uniquely sensitive to therapies that target tumor blood vessels.

A novel avenue of treatment for subtypes of bladder cancer builds on Nobel Prize-winning work by a Johns Hopkins scientist, Gregg Semenza, M.D., Ph.D., who described how tissues respond to low oxygen concentrations (hypoxia).

It turns out that hypoxia happens in some aggressive forms of bladder cancer, as well. As part of their discovery of the basal and luminal molecular subtypes of bladder cancer, Brady scientists Woonyoung Choi, M.S., Ph.D., and David McConkey, Ph.D., Director of the Johns Hopkins Greenberg Bladder Cancer Institute and the Erwin and Stephanie Greenberg Professor of Urology, recognized that “basal bladder cancers express genes associated with the low-oxygen pathway discovered by Dr. Semenza and his colleagues,” says McConkey.

Working with UK scientist Catharine West, Ph.D., and her colleagues in Manchester, Choi and McConkey confirmed that low-oxygen gene expression is associated with more aggressive and fatal cancers, and that a class of biomarkers known as microRNAs can be used to identify these tumors. In an exciting collaborative project with Johns Hopkins scientist Daniele Gilkes, who trained with Semenza, along with investigators at Memorial Sloan-Kettering Cancer Center, Dana-Farber Cancer Institute, and Duke University, the Brady team is investigating “whether tumors that display low-oxygen gene expression are uniquely sensitive to therapies that target tumor blood vessels,” says Choi. Two recently-completed Phase 3 clinical trials, based on the pivotal results of a Phase 2 clinical trial – led by oncologist Noah Hahn, M.D. – of gemcitabine/ cisplatin plus bevacizumab (a therapy that targets tumor blood vessels), confirmed that “these agents extend some patients’ lives,” says McConkey. The team’s research also suggests that oxygen-related biomarkers can determine which patients are likely to benefit from blood vessel-targeted therapies.

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