Development of Novel Chemotherapeutic Approaches in a Pediatric Glioma Model
- McAnulty, Tatiana K.
- [University Park, Pennsylvania] : Pennsylvania State University, 2021.
- Physical Description:
- 1 electronic document
- Additional Creators:
- Keiler, Kenneth C. and Schreyer Honors College
- Restrictions on Access:
- Open Access.
- Diffuse intrinsic pontine glioma (DIPG) is an aggressive pediatric brain cancer that is characterized by a low survival rate. This dismal prognosis is due in part to the difficulty with which the cancer is treated. Not only is DIPG resistant to commonly used chemotherapeutic agents, but its location in the brain and infiltrative nature cause full surgical resection to be a rarity. With such a resistance to treatment and aggressive growth, there is a pressing need for the development of novel therapeutics for this disease. In response to this demand, one compound, known as ONC201, was discovered to decrease the size of DIPG tumors and studied to better understand its anticancer mechanism within the cells. The ensuing work presents a dose-dependent reduction of both DIPG tumor cell viability and concentration of the mitochondrial transcription factor A (TFAM). Together, such results suggest that ONC201 acts to hyperactivate the mitochondrial ClpP protease within the DIPG tumor cells. This presumed mechanism of action will be later confirmed with strains expressing either an inactive or a constitutively active ClpP enzyme. Further efforts to discover novel compounds with activity similar to that of ONC201 led to the identification of two crude natural products with the ability to reduce the growth of cultured DIPG tumor cells. Future purification of these natural products will facilitate the characterization of the active component allowing for the anticancer activity within these natural products. Activation of the ClpP protease stands as a therapeutic mechanism not only for cancers but also for infections caused by multidrug resistant bacterial species; thus, the presented results hold great potential for the discovery of new treatments for both disease circumstances.
- Dissertation Note:
- B.S. Pennsylvania State University 2021.
- Technical Details:
- The full text of the dissertation is available as an Adobe Acrobat .pdf file ; Adobe Acrobat Reader required to view the file.
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