Advisor(s)
Anna Sorace
Committee Member(s)
Jullienne Carstens
Suzzane Lapi
School
Joint Health Sciences (Interdisciplinary)
Document Type
Thesis
Department (new version)
Joint Health Sciences
Date of Award
9-9-2024
Abstract
Triple negative breast cancer (TNBC) makes up 10-20% of breast cancer cases. Even with advancements in science, TNBC is treatment resistant due to the lack of any type of hormonal receptors on the cell surface making it difficult for targeted hormonal therapy. New research avenues have led to studies of the Tumor-microenvironment (TME) in detail. TME is a complex network of stromal cells, extracellular matrix (ECM) and cancer associated fibroblasts (CAFs) with pro-tumorigenic properties and plays a major role in tumor growth. Fibroblast activation protein (FAP) is a marker of CAF and promotes ECM remodeling through several pathways and has become of growing interest for targeted therapeutic strategies in several types of cancers. Theranostics is a new approach for targeted therapy using radionuclides which combines diagnostics and therapeutics. This approach includes a radionuclide radiolabeled with a peptide, antibody, chemotherapy drug, etc. for not only diagnosing using nuclear imaging techniques such as positron emission computed tomography (PET), single photon emission computed tomography (SPECT) and computed tomography (CT), but also for targeted radionuclide therapy by conjugating the radionuclides with proteins, peptides, antibodies, chemo drug, etc. which causes increase in DNA damage and increase in immune cell infiltration causing reduction in tumor burden. There are several radionuclide pairs currently in clinical trials for targeted radionuclide therapy (TRT), but none have matching diagnostic and therapeutic radioisotope pair. The objective of this study is to develop a theranostic approach using [64/67Cu]-radionuclides targeting FAP in TNBC combined with immunotherapy (IMT). Compared to the other radionuclide pairs, 64/67Cu not only has radio chemically paired but 67Cu also has proven to be more effective than other beta emitting radionuclides. Keywords: tumor microenvironment (TME), cancer associated fibroblasts (CAF), fibroblast activation protein (FAP), theranostics, targeted radionuclide therapy (TRT), [64/67Cu].
ProQuest ID
Recommended Citation
Sharmila Sridhar, Fnu, "Combination Of 64/67Cu Theranostics And Immunotherapy Targeting Fibroblast Activation Protein In Triple Negative Breast Cancer" (2024). All ETDs from UAB. 7637.
https://digitalcommons.library.uab.edu/etd-collection/7637
