New Research Disrupts Cancer's Feeding Cycle

Keeping cancer cells from the fat they need to grow: researchers' work brings detours from the lab… to dairy barns and gyms.

Focus article photo

Nancy Kuemmerle, D.O., Ph.D., is an assistant professor of medicine at The Geisel School of Medicine at Dartmouth, and an oncologist at the White River Junction Veterans Administration hospital.

NCCC research targets fatty acid synthesis in breast cancer

The goal of most cancer treatments−surgery, radiation, or chemotherapy−is to eliminate cancer cells in the body. NCCC researchers like Dr. William Kinlaw, professor of medicine at The Geisel School of Medicine at Dartmouth, and Nancy Kuemmerle, a Geisel School of Medicine assistant professor of medicine and VA hospital oncologist, are collaborating with other physicians and scientists to find ways to kill cancer cells by disrupting the processes that create the fats they need to grow and spread.

An article published in the February 2013 issue of Breast Cancer Research and Treatment reports on a recent NCCC clinical trial that shows how treatment targeting key genes involved in fatty acid synthesis may significantly reduce the growth of invasive breast cancer tumors. This work offers insights into how new therapies might be used to kill breast cancer cells.

Scientists focus on how cancer cells create the fats they need to grow

William Kinlaw, M.D., professor of medicine at
The Geisel School of Medicine at Dartmouth

In the early 1980s Kinlaw's thyroid research at University of Minnesota uncovered a previously undiscovered gene, Spot 14. Subsequent studies showed that Spot 14 was expressed by breast cancer cells, and also seemed to be connected to how these cells produced fatty acids. In recent years Kinlaw has zeroed in on fatty acid synthesis, and how targeting the genes involved in this process might provide new ways to "starve" cancer cells. 

In a 2006 study, Kinlaw's work with Geisel School professor Wendy Wells found that aggressive breast cancer tumors had a high expression of Spot 14. Patients with these tumors also had high recurrence rates, suggesting that the tumors with high Spot 14 expression were better at synthesizing the fatty acids they depend on.

Additional work on fatty acid synthesis by Kuemmerle suggests that breast cancer tumors also extract fatty acids directly from the environment. She is currently studying the fatty acid metabolism in liposarcomas. "Liposarcomas are a great model system because they synthesize fatty acids, and they obtain them from dietary lipids in the blood circulation," she said.

A Cornell researcher's questions about cow's milk reveal new paths

In 2009 Kinlaw received a call from Dale Bauman, Liberty Hyde Bailey Professor at Cornell, who was studying milk fat depression syndrome, a condition where dairy cows produce milk that contains no fat. Bauman was puzzled to find a correlation between milk fat production and the amounts of Spot 14 found in mammary gland biopsies of the cows producing the milk.

He knew little about Spot 14, but had read of Kinlaw's work.  Kinlaw was intrigued that Bauman had identified a substance, conjugated linoleic acid (CLA), that shut down fatty acid synthesis cows.

"After a series of discussions we both came to the same question," Kinlaw said. "If CLA can shut down fat production in normal mammary cells, can it also do it in breast cancer?"

Bodybuilding supplement jump-starts clinical trial process

CLA is sold in health food stores as a dietary supplement (used for weight loss and body building), and researchers at the University of Wisconsin had published studies on CLA and weight loss. Because of this, the NCCC team could avoid the time and expense involved in preliminary trials to establish safe dosage levels in humans.

Possible prototype for drugs to target breast cancer tumors

In the NCCC clinical trial that studied CLA, 24 women already diagnosed with breast cancer were treated with CLA during the 10-12 days between the initial biopsy and surgery to remove the tumor.

CLA concentration levels were measured at the beginning and end of the trial, and the biopsy tissue samples (pre CLA) and surgically removed tumor tissue samples (post CLA) were also studied. They found that CLA may be a prototype for drugs that suppress the expression of key genes cancer cells use to get the fatty acids they need to survive.

The complete report can be found in the February 2013 issue of Breast Cancer Research and Treatment or on NCBI: "A Proof of Purpose Clinical Trial to Determine Whether Conjugated Linoleic Acid Modulates the Lipogenic Pathway in Human Breast Cancer Tissue."

March 11, 2013