Publications by authors named "Sara Durland-Busbice"
Article Synopsis
- LY2334737 is an oral prodrug of gemcitabine that, upon absorption, releases gemcitabine and valproic acid, achieving higher plasma levels and prolonged exposure compared to gemcitabine alone.
- The drug demonstrated significant antitumor activity in mouse models of human colon and lung tumors with metronomic dosing schedules, where a daily dose of 6 mg/kg for 21 days was as effective as the traditional intravenous administration of gemcitabine at 240 mg/kg.
- Combining LY2334737 with capecitabine showed improved efficacy in colon xenografts, highlighting the potential for enhanced treatment outcomes through the co-administration of these prodrugs, particularly in tumors with elevated CES2 or ENT
Purpose: The oral prodrug of gemcitabine LY2334737 is cleaved systemically to gemcitabine; the mechanism responsible for hydrolysis is unknown. LY2334737 cytotoxicity was tested in the NCI-60 panel; mining of microarray expression data identified carboxylesterase (CES) as a top hydrolase candidate. Studies examined whether CES is responsible for hydrolysis and whether cellular CES expression confers prodrug sensitivity.
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