SYNOPSIS: Metastatic prostate cancer is treated with androgen deprivation therapy (ADT), which involves the maximal suppression of circulating testosterone. Although initial responses are generally favorable, most cases progress to metastatic castration resistant prostate cancer (mCRPC), which is refractory to standard ADT. Our goal is to develop a treatment strategy to improve response of mCRPC by combining a clinically utilized metabolic modulator, AZD3965, with docetaxel. AZD3965 effects were measured in vivo by 31P and 1H MRS in PC3 prostate cancer xenografts. In vitro results suggest that AZD3965 enhances the growth inhibitory effect of docetaxel similarly both in PC3 and LNCaP cells although PC3 expresses both MCT1 & 4 and LNCaP only expresses MCT1.
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