Advisor(s)
Anna Sorace
Committee Member(s)
Anita Hjelmeland
Benjamin Larimer
Christopher Willey
Jason Warram
School
Joint Health Sciences (Interdisciplinary)
Document Type
Dissertation
Department (new version)
Biomedical Engineering
Date of Award
6-4-2025
Abstract
Breast cancer remains a leading cause of cancer-related mortality in women, with HER2+ and triple-negative breast cancer (TNBC) subtypes exhibiting aggressive progression and high metastatic potential. While advances in targeted therapy and immunotherapy have improved patient outcomes, treatment resistance and disease recurrence persist as significant clinical challenges. This dissertation explores the role of radiation therapy in modulating the tumor microenvironment to enhance therapeutic efficacy, focusing on mechanisms underlying radiation-induced immune modulation and radiation in combination with targeted therapy. We investigate how HER2-targeted therapies influence tumor oxygenation and DNA damage response to potentiate the effects of radiation therapy. Utilizing preclinical models, we demonstrate that trastuzumab enhances radiation-induced tumor cell death by increasing DNA double-strand breaks and mitigating hypoxia, as assessed through [18F]-fluoromisonidazole (FMISO) PET imaging. Furthermore, we expand our molecular imaging approaches to explore the relationship of radiation and immune infiltration. CD8 targeted immune-PET imaging reveals that radiation therapy can promote CD8+ T-cell infiltration, allowing for stratification in the treatment of combination radiation + immunotherapy in TNBC. Finally, this work examines the therapeutic potential of HER2-targeted radionuclide therapy, offering a precision medicine approach to treating HER2+ metastatic breast cancer. Through molecular imaging, transcriptomic analyses, and in vivo studies, this dissertation highlights novel therapeutic strategies that integrate targeted agents, radiation therapy, and immune modulation to improve cancer treatment outcomes. Our findings support a shift toward leveraging the tumor microenvironment to enhance treatment response, paving the way for future investigations into mechanistic interactions between radiation, tumor hypoxia, and immune activation.
ProQuest ID
Research Approval
Modification Approval Notice.pdf (32 kB)
Research Approval
Recommended Citation
Song, Patrick, "Targeting Radiation Induced Tumor Immune Microenvironment Modulation In Breast Cancer" (2025). All ETDs from UAB. 7330.
https://digitalcommons.library.uab.edu/etd-collection/7330
