R01 Equivalent Research Project
Prostate cancer (PCa) is the second leading cause of cancer death in the United States among men and it is more common in African American males. Despite initial good responses to androgen deprivation or anti-androgen drugs, tumors invariably recur and develop into lethal castration resistant prostate cancer (CRPC). Currently, the available therapeutic options for CRPC, including the gold standard chemotherapy docetaxel, have only met with limited success. The 52 kDa FK506 binding protein (FKBP52) is a promising strategy for novel targeted therapeutic development. MJC13 and GMC1, two first-in-class drugs that specifically inhibit FKBP52-mediated potentiation of AR signaling, have been discovered by Dr. Cox at University of Texas at El Paso and further developed by Dr. Xie at Texas Southern University. And US patents have awarded for the compounds and their formulations to Drs. Cox and Xie. The exciting anti-tumor efficacy observed in CRPC xenograft animal models encourage us to further develop novel targeted nano-drug delivery systems (NDDS) that specifically deliver MJC13 and GMC1 to the tumor site then steadily release the drug to facilitate synergistic effect with docetaxel to treat CRPC.
Our aims are to develop folic acid (FA)-conjugated NDDS of MJC13 and GMC1 for specific tumor targeting, high efficacy and low off-target adverse reactions; to perform comprehensive in vivo pharmacokinetic and pharmacodynamic evaluations on the optimal NDDS of MJC13 and GMC1; to investigate combination therapy of MJC13 and GMC1 and docetaxel in comparison to the marketed anti-AR drug enzalutamide. We will use various techniques, rats, tumor xenograft mouse models and genetically engineered mouse models to conduct those experiments in collaboration with experts at TSU and other institutions.
This project will seek support and evaluation from the CBMHR Administrative Core, will heavily utilize the Research Infrastructure Core to perform studies, and will disseminate the research findings from this project with various TSU communities via support from our Community Engagement Core (CEC). It will further enhance RCMI institutions’ prestige in the areas of biomedical and minority health research. The successful execution of this research will result potential advanced treatment for CRPC patients.
Huan Xie, Ph.D. (PI) Professor of Pharmaceutics, COPHS, TSU
Dr. Xie is a Professor of Pharmaceutics in the COPHS, with a strong background in drug characterization, formulation, novel delivery systems, pharmacokinetics and nanotechnology, focusing on preclinical drug development. she has the specific training, expertise, leadership and motivation to conduct the proposed project. Currently she is the PI of several grants, including the overall U54 RCMI grant and also serve as Director of GCC Center for Comprehensive PK/PD and Formulation (CCPF) supported by CPRIT. She had 4-year industrial experience as Senior Research Scientist working on silica/gold nanoshells for photothermal ablation cancer therapy, which has been in several cancer clinical trials. Since she joined TSU in 2008, she further applied her expertise to research.
In addition to her normal teaching load, she has successfully carried out over 30 research projects, taught over 1000 Pharm.D. students and personally mentored 5 research scientists/postdoctoral fellow, over 30 Ph.D., Pharm.D., and undergraduate students, most of them are under representative minorities (URM). Those trainees were highly sorted by employers including FDA, drug companies, hospitals and academia. She has also collaborated with various researchers from universities and companies across the nation. As PI or co-Investigator on several NIH- and private agent-funded grants, she laid the groundwork for the proposed research by developing novel analytical methods, advanced drug formulations and drug delivery systems, and establishing their pharmacokinetic and biodistribution profiles, as documented in the following publications and patents.