Resistance to cisplatin (CDDP)-based combination therapies makes advanced bladder cancer difficult to treat. UMUC3-control-short hairpin RNA (shRNA) cells with endogenous androgen receptor (AR) and AR-negative 647V/5637 cells stably expressing AR were more resistant to CDDP than UMUC-AR-shRNA and vector control cells, respectively. In AR-positive cells, treatment with R1881, a synthetic androgen, induced NF-κB expression (a mechanism of CDDP resistance). Furthermore, AR and NF-κB levels were increased in CDDP-resistant cells following long-term CDDP exposure. These data suggest that AR activation might be involved in CDDP resistance via a NF-κB mechanism, and that targeting AR might overcome CDDP resistance
References
Kashiwagi, E. N. et al. Androgen receptor activity modulates responses to cisplatin treatment in bladder cancer. Oncotarget http://dx.doi.org/10.18632/oncotarget.9994 (2016)
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Fenner, A. Cisplatin response is modulated by AR activity. Nat Rev Urol 13, 437 (2016). https://doi.org/10.1038/nrurol.2016.121
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DOI: https://doi.org/10.1038/nrurol.2016.121