Authors:
 Kareena M. Menezes, Victoria Mgbemena, Leah Bush, Huichen Wang, Dumitru Iacobas, Yoonsung Jung, Premkumar Saganti
 
 
 Affiliations:
 Prairie View A&M University
 
 
 Abstract Body:
 Prostate cancer (PCa) is a common malignancy and second leading cause of death among men. The disease exhibits a prominent racial disparity, with African-American men 1.4 times more likely to be diagnosed, presenting higher-grade tumors at the time of diagnosis, and 2-3 times higher risk of death from PCa than Caucasian men. However, the majority of PCa cells are derived from Caucasian men, and less than 10% African-American PCa patients are enrolled in existing clinical trials. The mechanisms underlying cancer development, metastasis, and treatment are underrepresented, understudied, and underfunded for African-American PCa patients. Radiation therapy is a standard treatment for localized and locally advanced disease, combined with androgen deprivation therapy. PCa is one of the cancers treated by particle cancer therapy to avoid cancer radioresistance and spare normal tissue. In order to study PCa disease etiology and disparity, our team proposes to use PCa cells derived from an African American patient (MDA PCa 2b) along with Caucasian-derived cells (LnCAP and PC-3) which vary in their degrees of invasiveness and utilize a Genomic Fabric Paradigm (GFP) approach to identify the Gene Master Regulator (GMR) for personalized cancer therapy. The central hypothesis of this proposal is that GMRs play a critical role in the disparity of cancer cell growth, metastasis, immune response, and treatment, and GMR-guided radiotherapy and immunomodulation will enhance the efficacy of radiation therapy in PCa treatment. To study radiation responses, we will examine cell growth, invasiveness, cell survival and associated signaling pathways, Epithelial-to-Mesenchymal Transition (EMT), senescence, apoptosis, autophagy, and DNA damage in PCa cells treated with X-rays, gamma rays, and protons at different radiation doses. For the GMR approach, we will identify biomarkers and GMR in racially disparate PCa cells and perform immunohistochemical analysis of a panel of protein markers and DNA microarray of PCa cells with normal prostate cells (RwPE) as the healthy control. Lastly, the output from the above studies will be used to develop therapeutic targets to enhance the efficacy of cancer cell killing and reduce the toxic effect to normal cells. We will examine the carcinogenesis and cancer cell survival of radiation treatment combined with immune modulators, kinase inhibitors, and RNA drugs. The overall outcome of this application will reveal personalized GMR to predict PCa progression and response to treatment, provide a novel strategy of combination treatment, and reduce the underrepresentation of cancer treatment in African-American patients. We have long-standing collaborations with national laboratories and radiation facilities for proton and gamma-ray studies at various energies and our own 350 kV X-ray as well as GMR facility on our premises to conduct this study. Finally, as an HBCU our primary demographic is African-American, and as such we have a particularly strong commitment to this study.
 
 
 Funding Acknowledgments:
 Available funds from the Chancellor's Research Initiative/Radiation Institute for Science & Engineering
 
 
 Corresponding Author Email:
 kmmenezes@pvamu.edu
 
 
 Conflict of Interest:
 Nothing to Disclose

Designing novel radiation protocols and drugs for prostate cancer using the Genomic Fabric Paradigm