Issues

Inflammation and epidermal growth factor receptor (EGFR) signaling dysregulation play an important role in urinary bladder cancer development. Non-steroidal anti-inflammatory drugs (NSAIDs) and EGFR inhibitors may block bladder tumorigenesis. However, daily dosing of either NSAIDs or EGFR inhibitors can cause gastrointestinal ulceration and acneiform rash, respectively, limiting their continuous use in a clinical prevention setting. To explore the utility of alternative dosing and scheduling of combination regimens, Mohammed and colleagues (in a study beginning on page 273) evaluated chemopreventive efficacy of pulsatile dosing of EGFR inhibitor erlotinib (once/week) combined with intermittent (3 weeks on/off) or continuous low doses of the NSAID naproxen in the OH-BBN induced rat bladder cancer model. All combination regimens tested, including late intervention with intermittent low-dose naproxen and weekly erlotinib combination, exerted robust antitumor effects. These findings demonstrate that significant chemopreventive efficacy could be achieved with alternative intervention regimens designed to reduce the toxicity of agents, and that starting the combination treatments at the time microscopic tumors were present still conferred the efficacy. The photograph on the cover shows a typical histological image of transitional cell carcinoma in the urinary bladder of an untreated female Fischer-344 rat exposed to the carcinogen OH-BBN.