Date of Award

8-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Healthcare Genetics

Committee Chair/Advisor

Luigi Boccuto

Committee Member

Diana Ivankovic

Committee Member

Christopher Farrell

Committee Member

Hakon Hakonarson

Abstract

Breast cancer remains one of the most prevalent diseases worldwide, yet therapeutic equity is still lacking. Standard treatments including surgery, radiotherapy, chemotherapy, and long-term hormone therapy. These approaches are often accompanied by significant side effects. While newer methods such as immunotherapy and targeted therapies have emerged, chemotherapy protocols and incorporation have remained largely unchanged in the past decades. In this context, nutraceuticals represent an alternative or adjuvant to therapy worthy of exploration. The reviewed literature highlights the anti-carcinogenic activity in selected nutraceuticals, marjoram, thyme and persimmon, considering their phytochemical constituents and secondary metabolites. Metabolomic profiling using the Biolog Phenotype Mammalian Microarray (PM-M) system reveals unique metabolic fingerprints of breast cancer cells, both at baseline and in response to chemotherapy (doxorubicin). The analysis includes breast cancer subtypes derived from primary tumor origins, metastatic sites, and those defined by molecular features including strong estrogen and progesterone-positive, and triple-negative status. Plates PM-M1 to PM-M4 reveal distinct patterns energy utilization from sole sources present in the well. Plates PM-M5 to PM-M-8 evaluate the cellular responses to effectors such as hormones, growth factors and ions in a dynamic response measuring capacity. In these last plates, the breast cells have the same uniform energy source, glucose. These findings reveal subtype-specific metabolic shifts, suggest preliminary biomarkers, and set the stage to test other therapeutics and their effects on healthy cells, such as the selected nutraceuticals. Nutraceuticals may play a pivotal role in expanding access to more affordable, safer, and standardized treatment options. From an ethical standpoint, promoting research in this area aligns with efforts to advance therapeutic equity by expanding access to therapeutics and comprehensive care for breast cancer patients. A health policy framework is proposed, encompassing a breast cancer task force, an online access tool, and integration of research into care. This offers a path in the backdrop of an urbanizing United States towards unifying the delivery of rural and urban breast cancer care. Nutraceuticals are revealed through this body of work to have a multitude of positive biological effects and promising anticancer properties; the metabolomic findings presented include distinct subtype-specific therapeutic signatures and biomarkers, and the ethical analysis supports a pathway toward equitable, globally applicable breast cancer treatment.

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