ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
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Description
Cancer is a disease of multicellularity, with deep evolutionary origins. As such, the forces of both evolution and natural selection operate on multiple scales to govern tumor dynamics. As multicellular organisms increase in complexity, cellular-level fitness must be controlled in order to maintain organismal-level fitness. Mutations that might provide a benefit at the cellular level by allowing for rapid proliferation are subject to the same forces that function on the organismal level, wherein cancer suppression is a benefit – especially as organisms increase their body size and lifespan. In order to maintain these large cellular bodies and long lifespans, organisms must increase their means of cancer suppression, and it is likely that these two phenomena co-evolved together. On a smaller scale, the cooperative dynamics of circulating tumor cell (CTC) clusters engage in cooperation to form networks of connected single cells that provide protection, stability, and cooperative sharing of resources to enhance their survival as they detach from a primary tumor and metastasize at secondary sites. This work seeks to explore the phenomenon of multi-level selection in neoplastic disease by examining A) the mechanisms of cancer suppression at multiple scales, B) the ecological resilience and stability of cooperating cellular clusters and C) a large-scale dataset on cancer prevalence across mammals, sauropsids (birds and reptiles), and amphibians, illuminating the evolutionary life history characteristics that explain the tradeoffs between cancer suppression and overall organism fitness. By taking an ecological and evolutionary approach to understanding cancer, novel strategies of cancer treatment may be discovered alongside fundamental discoveries about the fundamental forces of selection that govern evolutionary dynamics from the cellular to the organismal scale.
ContributorsHarris, Valerie (Author) / Maley, Carlo C. (Thesis advisor) / Aktipis, Athena (Committee member) / Boddy, Amy M. (Committee member) / Compton, Carolyn (Committee member) / Arizona State University (Publisher)
Created2022
Description
Evolutionary theory provides a rich framework for understanding cancer dynamics across scales of biological organization. The field of cancer evolution has largely been divided into two domains, comparative oncology - the study of cancer across the tree of life, and tumor evolution. This work provides a theoretical framework to unify these subfields with the intent that an understanding of the evolutionary dynamics driving cancer risk at one scale can inform the understanding of the dynamics on another scale. The evolution of multicellular life and the unique vulnerabilities in the cellular mechanisms that underpin it explain the ubiquity of cancer prevalence across the tree of life. The breakdown in cellular cooperation and communication that were required for multicellular life define the hallmarks of cancer. As divergent life histories drove speciation events, it similarly drove divergences in fundamental cancer risk across species. An understanding of the impact that species’ life history theory has on the underlying network of multicellular cooperation and somatic evolution allows for robust predictions on cross-species cancer risk. A large-scale veterinary cancer database is utilized to validate many of the predictions on cancer risk made from life history evolution. Changing scales to the cellular level, it lays predictions on the fate of somatic mutations and the fitness benefits they confer to neoplastic cells compared to their healthy counterparts. The cancer hallmarks, far more than just a way to unify the many seemingly unique pathologies defined as cancer, is a powerful toolset to understand how specific mutations may change the fitness of somatic cells throughout carcinogenesis and tumor progression. Alongside highlighting the significant advances in evolutionary approaches to cancer across scales, this work provides a lucid confirmation that an understanding of both scales provides the most complete portrait of evolutionary cancer dynamics.
ContributorsCompton, Zachary Taylor (Author) / Maley, Carlo C. (Thesis advisor) / Aktipis, Athena (Committee member) / Buetow, Kenneth (Committee member) / Nedelcu, Aurora (Committee member) / Compton, Carolyn (Committee member) / Arizona State University (Publisher)
Created2023