Targeting the Central Dogma to Inhibit Nodes of Convergence in Cancer

Cancer treatments often target singular oncoproteins in attempt to block one hallmark of cancer and stop tumor growth and progression. However, although these treatments are often initially effective, many cancer patients develop resistance and experience relapse due to redundant signaling or tumor heterogeneity. To avoid resistance mechanisms, cancer treatments must inhibit multiple hallmarks of cancer, and therefore multiple oncogenic signaling programs. One possible way to achieve this is to target nodes of convergence of oncogenic signaling, in which multiple oncogenic pathways depend on one protein for expression or signal proliferation. These nodes can be found within the central dogma processes that drive all cellular function. In this dissertation, this strategy is used to discover inhibitors of nodes involved in transcription, translation, and protein folding of oncogenes and oncoproteins. Targeting nodes of convergence may yield inhibitors that evade resistance mechanisms that plague current cancer therapies and provide superior clinical outcomes for cancer patients.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Graduate College

Grantor dc:publisher

The University of Arizona.

Year dc:date.issued

2021

Author dc:creator

• Zerio, Christopher

Advisor dc:contributor.advisor

• Chapman, Eli

Committee members dc:contributor.committeemember

• Zhang, Donna D.
• Wang, Jun
• Njardarson, Jon T.
• Tomasiak, Thomas M.

• BET
• Cancer
• Central Dogma
• Drug Discovery
• eIF4A
• Hsp70

Statement dc:rights

• Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction, presentation (such as public display or performance) of protected items is prohibited except with permission of the author.

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

en

Handle dc:identifier.uri

http://hdl.handle.net/10150/662570

OAI identifier oai:identifier

oai:repository.arizona.edu:10150/662570