In the United States, it is estimated that over 200,000 women will be diagnosed with
breast cancer and nearly 40,000 women will die of breast cancer in 20161. Mortality
from breast cancer is almost always attributed to metastatic spread of the disease to
other organs, thus precluding resection as a treatment method.2 Unfortunately,
conventional chemotherapy fails to eradicate many aggressive breast cancers. Studies
over the past decade have uncovered certain breast cancer cell-types, such as
estrogen/progesterone/human epidermal growth factor receptor 2 (ER/PR/ HER2)-
negative (triple-negative) breast cancers (TNBCs) that show poor prognosis and
chemotherapy resistance within breast tumors.3–5 Eliminating these breast cancer types
is critical in reducing the mortality associated with breast cancer. Current therapeutic
strategies for breast cancer include resection, nonspecific therapies such as radiation or
chemotherapy, and targeted strategies for combating certain types of breast cancers.
However, there are no targeted strategies for combating the most aggressive types of
breast cancers, including TNBCs.
Cancer cells are known to possess altered metabolism that fuels their malignancy and
pathogenicity. Most of what has been known about cancer cell metabolism focuses on
the well-characterized central carbon pathways, however, the mapping of the human
genome revealed that cellular metabolic networks extend far beyond that. In this
dissertation I present some extensions of our understanding of dysregulated cancer cell
metabolism in areas of lipid metabolism and membrane glycosylation. Furthermore,
using drugs and drug candidates already in clinical trials or the clinic, I identify new
metabolic targets that, when inhibited, contribute to or are responsible for killing TNBC
cells. Increasing our understanding of cancer cell metabolism, especially in the context
of small molecule inhibitors, will hopefully enable or promote the development of
targeted therapeutics for these highly lethal and poorly treated cancers.
