Researchers with The Cancer Genome Atlas (TCGA) Research Network have discovered key genes and pathways impacted by bladder cancer, unseen in previous studies. Several of these genes and pathways are also identified with other forms of cancer, suggesting that existing and developing targeted therapies could also be applied to the treatment of bladder cancer.
In a study published online on January 29 in Nature, researchers examined 131 patients with muscle-invasive bladder cancer who had not yet been treated with chemotherapy. In evaluating DNA, RNA, and protein data from the patients, recurrent mutations were found in 32 genes, including nine previously unknown mutations. Almost half the tumor samples contained mutations in the TP53 gene and 44% had mutations in the RTK/RAS pathway (commonly affected in cancers).
The research also discovered that genes regulating chromatin were more frequently mutated in bladder cancer than in any other common form of cancer that has been studied to date. This suggests that therapies targeting alterations in chromatin remodeling could be developed as potential therapy. In addition, potential drug targets were identified in 69% of the tumors in the study with frequent mutations in the ERBB2, or HER2, gene, FGFR3 gene, and in the PI3-kinase/AKT/mTOR pathway. Because these are also implicated with other forms of cancer, new agents under development against other forms of cancer could be effective in treating subsets of bladder cancer patients as well.
TCGA is a collaboration jointly supported and managed by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both parts of the National Institutes of Health.
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