UC Berkeley

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.