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Bladder Cancer Study Reveals Potential Drug Targets

Researchers find similarities to other cancers (January 29)

Investigators with The Cancer Genome Atlas (TCGA) Research Network have identified new potential therapeutic targets for a major form of bladder cancer, including important genes and pathways that are disrupted in the disease. They also discovered that, at the molecular level, some subtypes of bladder cancer resemble subtypes of breast, head-and-neck, and lung cancers, suggesting similar routes of development.

In the new study, published online in Nature, researchers analyzed DNA, RNA, and protein data generated from 131 muscle-invasive bladder cancers in chemotherapy-naive patients. The scientists found recurrent mutations in 32 genes, including nine that were not previously known to be significantly mutated. They discovered mutations in the TP53 gene in nearly half of the tumor samples, and mutations and other aberrations in the RTK/RAS pathway (which is commonly affected in cancers) in 44% of tumors. TP53 makes the p53 tumor-suppressor protein, which helps regulate cell division. RTK/RAS is involved in regulating cell growth and development.

Overall, the researchers identified potential drug targets in 69% of the tumors evaluated. They found frequent mutations in the ERBB2 (HER2) gene. The researchers also identified recurring mutations as well as fusions involving other genes, such as FGFR3, and the PI3-kinase/AKT/mTOR pathway, which help control cell division and growth and for which targeted drugs already exist.

“It is increasingly evident that there are genomic commonalities among cancers that we can take advantage of in the future,” said Eric D. Green, MD, PhD, Director of the National Human Genome Research Institute. “TCGA is providing us with a repertoire of possibilities for developing new cancer therapeutics.”

Source: NIH; January 29, 2014.

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