How bladder cancer originates and progresses has been illuminated as never before in a study led by researchers at Weill Cornell Medicine and the New York Genome Center. The researchers found that antiviral enzymes that mutate the DNA of normal and cancer cells are key promoters of early bladder cancer development, and that standard chemotherapy is also a potent source of mutations. The researchers also discovered that overactive genes within abnormal circular DNA structures in tumor cells genes drive bladder cancer resistance to therapy.
These findings are novel insights into bladder cancer biology and point to new therapeutic strategies for this difficult-to-treat cancer. The study, published Sept. 9 in Nature, focused on the main form of bladder cancer, urothelial carcinoma, which originates from cells that line the bladder, urethra, and tubes that drain urine from the kidneys.
The researchers examined malignant and pre-malignant urothelial cells taken from the same set of patients at different disease stages. They used whole-genome sequencing and advanced computational methods to map common DNA mutations, complex structural variants, and their timing. "Our findings define new fundamental mechanisms driving bladder cancer evolution—mechanisms that we can now think about targeting with therapies," said co-senior author Dr.
Bishoy Faltas, the Gellert Family-John P. Leonard MD Research Scholar in Hematology and Medical Oncology and an associate professor of medicine and of .