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Development of Novel Therapeutics Targeting Splicing Machinery in Ovarian Cancer

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Title: Development of Novel Therapeutics Targeting Splicing Machinery in Ovarian Cancer
Author(s): Arslan, Ahmet D.
Advisor(s): Beck, William T.
Contributor(s): He, Xiaolong; Mo, Yin-Yuan; Rong, Lijun; Wang, Zaijie J.
Department / Program: Biopharmaceutical Sciences
Graduate Major: Biopharmaceutical Sciences
Degree Granting Institution: University of Illinois at Chicago
Degree: PhD, Doctor of Philosophy
Genre: Doctoral
Subject(s): PTB Ovarian Cancer Alternative Splicing Cell-based High Throughput Screening polypyrimidine tract-binding protein
Abstract: Aberrations in alternative splicing of pre-mRNA splicing have been linked to many human malignancies, yet the mechanisms for these tumor-specific changes remain underexplored and represent a promising area for therapeutic intervention. We have reported the overexpression of a splicing factor, polypyrimidine tract-binding protein 1 (PTBP1), in ovarian tumor epithelial cells compared to matched normal controls and have further shown that PTBP1 small interfering RNA–mediated down-regulation has an antitumor effect. Coordinately, the depletion of PTBP1 expression resulted in enhanced sensitivity of ovarian tumor cells to paclitaxel and cisplatin. These data support PTBP1 as a novel target for the treatment of ovarian cancer. However, no commercially available PTBP1 inhibitors have yet been described. To expand our ability to find novel inhibitors, we developed and implemented a robust cell-based high throughput screening assay for the discovery of small molecule modulators of PTB activity. The targeting of a splicing factor, such as PTBP1, represents an innovative approach for cancer therapeutics and provides a foundation for generating new lead compounds that specifically target the PTBP1 protein to be used in ovarian cancer therapy.
Issue Date: 2012-12-10
Genre: thesis
Rights Information: Copyright 2012 Ahmet D. Arslan
Date Available in INDIGO: 2012-12-10
Date Deposited: 2012-08

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