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Tumor Suppressor Genes Linked to Bladder Cancer

Treatment with rapamycin significantly slows progression of tumors in mice

THURSDAY, March 26 (HealthDay News) -- Inhibition of mammalian target of rapamycin (mTOR) signaling may offer a potential treatment for invasive bladder cancer, according to research published in the March 15 issue of Genes & Development.

Anna M. Puzio-Kuter, of Columbia University in New York City, and colleagues used a new mouse model to demonstrate that deletion of p53 and Pten in the bladder epithelium leads to invasive cancer. Research using human bladder tumors found that combined alterations of p53 and Pten are frequent in invasive disease and are linked to poor outcomes.

The investigators also found that p53 and Pten inactivation promotes deregulation of the mTOR signaling pathway in invasive cancers. Using the mouse model, they found that mice treated with vehicle developed large bladder tumors, but mice treated with rapamycin as a prevention strategy had normal bladders free of obvious abnormality.

"Our findings provide a strong rationale for therapeutic targeting of the mTOR signaling pathway in invasive bladder cancer, particularly in patients having deregulated p53 and PTEN, as well as a preclinical model for effective assessment of appropriate therapies. Notably, clinical successes with rapamycin analogs as single agents have been limited, with some notable exceptions. In contrast, rapamycin analogs have been shown to be more promising in combination with standard chemotherapy or agents that target other signaling pathways, particularly the RAS/MEK/MAP kinase pathway," the authors write.

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