Understanding liver metabolic effects of estrogens and liver niche-related metabolic changes in metastatic breast cancer

Breast cancer is the most prevalent cancer in women worldwide. While the five-year survival rate for women with localized breast cancer is more than 90%, for those with metastatic breast cancer is 28%, and the median overall survival of those is only 2–3 years. One of the common sites for ER+ metastatic breast cancer (MBC) is the liver. For patients with breast cancer liver metastases that are not treated, survival is as low as 4–8 months. Improving the survival of women with breast cancer requires more effective anti-cancer strategies, especially for metastatic disease. Nutrients can influence tumor microenvironments and manipulate cancer metabolism via a dietary modification to enhance anti-cancer strategies, so it is critical to optimize future investigations of metabolic therapies to understand how dietary factors and pharmacotherapies influence carcinogenesis based on tumor- and patient-related characteristics. In the first part of my Ph.D. studies, I developed a deeper understanding of the liver metabolic effects of estrogens and how estrogens regulate non-alcoholic fatty liver diseases (NAFLD) while providing a high-fat diet. I identified a novel estrogen compound, pathway preferential estrogens, which provides benefits like hormone replacement therapy (HRT) but without increasing reproductive cancer risk (Zuo, Q., et al. Nutrients, 2021). By writing the review (Zuo, Q., et al. Endocrinology, 2021) on obesity and postmenopausal hormone receptor-positive breast cancer and being involved in the project (Madak-Erdogan et al. Cancer Research, 2019) on fatty acid metabolism in breast cancer, I had great interests in how diet and nutrition influence cancer metabolism. Based on the knowledge of liver metabolic effects of estrogens and cancer-related methodologies, I developed the project on possible metabolic rewiring mechanisms to improve endocrine therapy efficacy in breast cancer liver metastasis with novel pharmaceutical or dietary intervention. I elucidate liver niche-related metabolic changes in metastatic breast cancers. In vitro 3D liver metastatic niche models characterized the molecular changes, and in vivo experiments illustrated that a fasting-mimicking diet (FMD) provides a low glucose tumor microenvironment to enhance Fulvestrant (Fulv) therapeutic effectiveness (Zuo, Q., et al. Molecular Cancer Research, 2022; Zuo, Q., et al, Nutrients, 2022). Based on these studies, in the last part of my Ph.D. thesis project, I further analyzed how FMD alters glucose, glycogen, fatty acids, and ketones metabolic pathways in breast cancer liver metastases.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Food Science & Human Nutrition

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2022

Author dc:creator

• Zuo, Qianying

Contributors dc:contributor

• Madak-Erdogan, Zeynep
• Arthur, Anna
• Nelson, Erik Russell
• Anakk, Sayeepriyadarshini

• Non−alcoholic Fatty Liver Disease (nafld)
• Hepatosteatosis
• Pathway Preferential Estrogen 1 (pape−1)
• High−fat Diet
• Metabolic Health
• Breast Cancer Liver Metastasis
• Fasting-mimicking Diet

Statement dc:rights

• Copyright 2022, Qianying Zuo

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/117532

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F117532