Developing Novel Therapeutics Targeting Undifferentiated and Castration-Resistant Prostate Cancer Stem Cells
Technical Report,29 Sep 2014,28 Sep 2015
The University of Texas MD Anderson Cancer Center Smithville United States
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The main objective of this DOD-supported project is to identify and develop novel therapeutics to target the undifferentiated PSA-lo, castration-resistant PCSCs. We proposed to achieve this objective with two Specific Aims 1 To perform phage display library PDL screening in PSA-lo PCa cells to identify PCSC-specific homing peptides and 2 To perform unbiased drug library screening to identify novel PCSC-targeting chemicals. In the past year, we have made good progress in accomplishing the goals for both Aims. For Specific Aim 1, we have further characterized the JRM2 peptide. For Specific Aim 2, we have finished a targeted library screening to identify several compounds that could sensitize the AR-PSA- LNCaP cells. We have also started screening our UNIQUE PSA-lo CRPC cells against a Protein Kinase Inhibitor Collection that contains 750 compounds that target 140 kinases. In the second year, we shall continue several experiments in both Aims, especially testing the in vitro and in vivo cytotoxicities of the conjugated JRM2 peptide and finishing up screening and validating the kinase inhibitor library screening.