Focus: Genetic variant as a selection marker for anti-prostate stem cell antigen immunotherapy of bladder cancer

A monoclonal antibody against prostate stem cell antigen (PSCA) has emerged as a novel cancer therapy currently being tested in clinical trials for prostate and pancreatic cancers, but this treatment is likely to be efficient only in patients with PSCA-expressing tumors. The present study demonstrates that a genetic variant (rs2294008) discovered by bladder cancer genome-wide association studies is a strong predictor of PSCA protein expression in bladder tumors, as measured by two-sided multivariable linear regression (P = 6.46×10(-11); n = 278). The association pattern is similar in non-muscle-invasive tumors, stages Ta (P = 3.10×10(-5); n = 173) and T1 (P = 2.64×10(-5); n = 60), and muscle-invasive tumors, stages T2 (P =.01; n = 23) and T3/4 (P =.03; n = 22). The study suggests that anti-PSCA immunotherapy might be beneficial for bladder cancer patients with high tumor PSCA expression, which is statistically significantly associated with the presence of CT and TT genotypes of a common genetic variant, rs2294008. Future clinical studies will be needed to validate PSCA as a therapeutic target for bladder cancer.

Source: Genetic variant as a selection marker for anti-prostate stem cell antigen immunotherapy of bladder cancer. Kohaar I, Porter-Gill P, Lenz P, Fu YP, Mumy A, Tang W, Apolo AB, Rothman N, Baris D, Schned AR, Ylaya K, Schwenn M, Johnson A, Jones M, Kida M, Silverman DT, Hewitt SM, Moore LE, Prokunina-Olsson L (prokuninal@mail.nih.gov). J Natl Cancer Inst. 2013 Jan 2;105(1):69-73.

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http://jnci.oxfordjournals.org/content/105/1/69.full.pdf+html