Gene variant may serve as target for bladder cancer therapy

Researchers have found a genetic variant that is a strong predictor of expression of the prostate stem cell antigen (PSCA) protein in bladder cancer—a discovery that could improve treatment efficacy in this disease.

“The big payoff is that a simple genetic test can determine which patients could benefit from anti-PSCA therapy,” explained senior study author Ludmila Prokunina-Olsson, PhD, of the National Cancer Institute (NCI) Division of Cancer Epidemiology and Genetics in Bethesda, Maryland, in an NCI statement. The research appears in Journal of the National Cancer Institute (2013;105:69-73).

A monoclonal antibody against PSCA has emerged as a novel cancer therapy currently being tested in clinical trials for prostate and pancreatic cancers, but the treatment is likely to be efficient only in persons with PSCA-expressing tumors, wrote Prokunina-Olsson and colleagues in their report. The group now hopes that the antibody will be tested in persons with bladder cancer with the newly identified genetic variant, as such therapy could help reduce potentially harmful side effects and lower treatment costs.

In a previous study, the investigators found that a variant located in the PSCA gene on chromosome 8 was associated with susceptibility to bladder cancer. In their current work, they learned that the “T” nucleotide that comprises a gene variant called rs2294008 is a strong predictor of PSCA protein expression. The variant increases the delivery of PSCA to the cell surface, where the protein promotes tumor growth.

“The study suggests that anti-PSCA immunotherapy might be beneficial for bladder cancer patients with high tumor PSCA expression,” the authors concluded.

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