Strategies for targeting cancer: small molecules, epigenetics and drug design
Date
2020
Authors
Hassell, Kelly N., author
Crans, Debbie C., advisor
Brown, Mark A., advisor
Roess, Deborah, committee member
Menoni, Carmen, committee member
Journal Title
Journal ISSN
Volume Title
Abstract
Cancer has plagued our human population since its early characterizations as abnormal cells and tissues in the mid-1900s. Initial treatment models included surgical removal of cancerous tissues. In the late 1960s, surgical removal and localized radiation were the only available options for treatment until the development of chemotherapeutics. These chemical cocktail treatments, designed to kill cancer cells, started in the late-1900s and even today remain a major line of defense in fighting this disease. The goal of the research described in this dissertation was to investigate current methodologies and techniques used to treat cancer; treatments utilizing chemotherapeutics, small molecule interactions, metallocage drug delivery, epigenetics and protein activity inhibition. The first part of my research focused on the significance of Cisplatin as a chemotherapeutic. My findings indicate the unexpected speciation of platinum in the human body as a revelation to be utilized in novel drug design. In my reverse micelle study, the hydrolysis of the Schiff-base compound was observed to be dependent on the size of reverse micelles; resulting in partial phase selectivity. The reverse micelle model provided ample support for engineering various types of liposomal delivery options for insoluble compounds like Cisplatin. My metallocage research explored the idea of utilizing a self-assembling Cisplatin protective capsule with fluorophores, equipped to monitor real-time cancer cell death as well as drug delivery. My findings support the efficacy of metallocages for delivery of cancer therapeutics and the necessity for continued methodology development for clinical applications. The second part of my research focused on the use of epigenetics for gene expression regulation and protein activity inhibition. My findings reported the most recent status of drugs developed using histone deacetylases (HDAC) and histone deacetylases inhibitors (HDACi) for targeting specific cancers. And in my final chapter of SET-domain proteins, my research focused on comparing the methyltransferase activity inhibition of SMYD3 in two different cancer cells lines. The data showed the A549 lung cell line is slightly more sensitive to the SMYD3 activity inhibitor. This dissertation describes work that has increased our collective understanding of cancer therapeutics. Furthermore, it vastly supports future cancer treatment investigations utilizing both small molecules and bioinformatics.