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The combination of sorafenib and valproic acid was predicated on the basis that sorafenib activity is enhanced by HDAC inhibition (149, 150), whereas the addition of sildenafil was based on its ability to increase peroxynitrate levels and to block ABCB1 and ABCG2 drug-efflux pumps, thus increasing drug delivery to the tumor (114, 151)

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