The Current Role of Kynurenine Pathway Interventions in Oxidative Stress and Redox Homeostasis in the Context of Aging and Cancer

Cancer is the second-leading cause of death in the United States and in Europe. Age is the single highest risk factor for developing cancer, and more than half of cancer diagnoses occur after age 70. Most cancer therapeutics are studied in younger and healthier individuals, excluding the impact that age-related comorbidities may have in the initiation and progression of cancer. There is clearly a gap in knowledge in the cancer field about the complex relationship between the development of the disease and the molecular environment in old individuals. In recent years, the kynurenine pathway –the main route to metabolize tryptophan in the cell– has emerged as a therapeutic target in several age-related diseases, including cancer. Intermediate metabolites in the kynurenine pathway have immunological and redox properties that have been associated with cancer initiation, progression, and metastasis. Increased flux of tryptophan metabolism towards the kynurenine pathway has been positively correlated with age and age-related diseases. The necessity of building the bridge between aging and cancer research using this shared metabolic pathway will create new knowledge in the understanding of age-driven cancer development. My goal is to investigate the intricacies of the kynurenine pathway and its role in the initiation and progression of cancer at an advanced age. The long-term goal of my career is to develop therapeutic targets that prevent or delay the onset of cancer by improving cell fitness by targeting mechanisms in the underlying aging process. Delaying aging-associated decline is not only going to improve the wellbeing of older adults, but also reduces the burden costs of public health associated to the treatment of age-related comorbidities. The results of this project will provide, at an academic level, a deeper understanding of the correlation between age and cancer and, at a clinical level, the possibility of preventing cancer development by targeting the underlying biological processes that drive cellular and physiological functional decline with age.

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

2023

Author dc:creator

• Castro-Portuguez, Raul

Advisor dc:contributor.advisor

• Sutphin, George L.

Committee members dc:contributor.committeemember

• Smith, Catharine L.
• Zavros, Yana
• Padi, Megha
• Schnellmann, Rick

• aging
• cancer
• ferroptosis
• kynurenine pathway
• Nrf2
• oxidative stress

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/10150/669801

OAI identifier oai:identifier

oai:repository.arizona.edu:10150/669801