Pharmacodynamic distribution of docetaxel andcabazitaxel in prostate cancer xenografts, and evaluation of pantoprazole to enhance their activity
Chemotherapy drugs target and kill rapidly-dividing cells located closest to blood vessels, but do not penetrate deep into the tumor. Limited drug distribution in tumors is an important cause of drug resistance. A method to increase tumor drug delivery and combat resistance is the subject of this proposal. To counteract chemotherapy resistance, the use of an ulcer medication (pantoprazole) is being investigated. The objective of this proposal is to determine the drug effect of cabazitaxel using biomarkers that indicate where in the tumor a drug is working. The combination of pantoprazole with cabazitaxel will be investigated as a potential method to enhance drug delivery to tumor cells, thereby increasing the effects of cabazitaxel. These findings will be particularly valuable as they can be employed in designing strategies to overcome therapeutic resistance by modifying or complementing the limited spatial distribution of drug activity in solid tumors, and thereby increase therapeutic efficacy.