Year: 2017
Type: dissertation
Abstract: In the United States, it is estimated that over 200,000 women will be diagnosed withbreast cancer and nearly 40,000 women will die of breast cancer in 20161. Mortalityfrom breast cancer is almost always attributed to metastatic spread of the disease toother organs, thus precluding resection as a treatment method.2 Unfortunately,conventional chemotherapy fails to eradicate many aggressive breast cancers. Studiesover the past decade have uncovered certain breast cancer cell-types, such asestrogen/progesterone/human epidermal growth factor receptor 2 (ER/PR/ HER2)-negative (triple-negative) breast cancers (TNBCs) that show poor prognosis andchemotherapy resistance within breast tumors.3–5 Eliminating these breast cancer typesis critical in reducing the mortality associated with breast cancer. Current therapeuticstrategies for breast cancer include resection, nonspecific therapies such as radiation orchemotherapy, and targeted strategies for combating certain types of breast cancers.However, there are no targeted strategies for combating the most aggressive types ofbreast cancers, including TNBCs.Cancer cells are known to possess altered metabolism that fuels their malignancy andpathogenicity. Most of what has been known about cancer cell metabolism focuses onthe well-characterized central carbon pathways, however, the mapping of the humangenome revealed that cellular metabolic networks extend far beyond that. In thisdissertation I present some extensions of our understanding of dysregulated cancer cellmetabolism in areas of lipid metabolism and membrane glycosylation. Furthermore,using drugs and drug candidates already in clinical trials or the clinic, I identify newmetabolic targets that, when inhibited, contribute to or are responsible for killing TNBCcells. Increasing our understanding of cancer cell metabolism, especially in the contextof small molecule inhibitors, will hopefully enable or promote the development oftargeted therapeutics for these highly lethal and poorly treated cancers.
Author: Lindsay S. Roberts
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2748223821