Author ORCID Identifier
Date of Award
2026
Document Type
Thesis (Ph.D.)
Department or Program
Cancer Biology
First Advisor
Todd W. Miller
Second Advisor
Kimberley S. Samkoe
Abstract
Estrogen Receptor-positive/ Human Epidermal Growth Factor 2-negative, breast cancer (ER+/HER2- BC) is the most prevalent subtype of BC, impacting millions of individuals. Although early screening and treatment with endocrine therapy has greatly enhanced survival, this subtype sustains a steady increase of risk for recurrent disease for decades after diagnosis, indicating the persistence of residual cancer cells that are capable of maintaining dormancy for >20 years prior to metastatic outgrowth. Dormant cells reprogram metabolic pathways which can be profoundly influenced by the tumor microenvironment in promoting quiescence or proliferation. Fatty acid oxidation dependency has been noted as a hallmark of drug tolerant persistent populations and lipid metabolism has been implicated in potentiating survival under stress, like endocrine therapy. The most frequent site of metastasis of the ER+/HER2- subtype is bone and there is a present need to identify vulnerabilities of dormant populations to reduce or delay the advent of overt, and ultimately fatal metastatic disease. We aim to add to a growing body of knowledge that implicates CD36-mediated lipid uptake as a potential therapeutic marker of and target for dormant ER+/HER2- BC. We utilized in vitro and in vivo models of dormancy as well as a novel, integrated bone niche specific, facilitated dormancy model. We utilized adipocyte coculture, conditioned media, and intra-tibial xenograft modeling to interrogate fatty acid metabolism targets. We performed functional metabolic seahorse assays, transcriptomic profiling with Bulk RNA sequencing, proteomics analysis, and animal modeling of human cancer lines in immune-suppressed mouse models. We found that CD36 is upregulated in xenograft models under hormone-deprivation induced dormancy and that CD36 blockade with anti-CD36 monoclonal antibody was able to reduce residual tumor burden in mammary fat pad model of dormancy, developed by Hampsch, et al., and in our adapted model of dormancy in bone. The significance of this work is in identifying CD36 as a marker of dormancy and a potential target for reducing dormant tumor burden, promoting the continued translation of CD36 as a viable therapeutic target in cancer.
Recommended Citation
Goen, Abigail E., "The Influence, Dependency, and Targeting of Fatty Acid Uptake in ER+ Breast Cancer" (2026). Dartmouth College Ph.D Dissertations. 513.
https://digitalcommons.dartmouth.edu/dissertations/513
