Researchers identify critical metabolic alterations in triple-negative breast cancer cells

Researchers at Fox Chase Cancer Center have identified a host of small molecules critical to metabolism in cells of triple-negative breast cancer - one of the least understood groups of breast cancer. These molecules, called metabolites, include key players in energy regulation and lipid synthesis. They could help pave the way for helping researchers differentiate among different forms of the disease and ultimately point to new targets for treatment.

Jeffrey Peterson, PhD, a cancer biologist at Fox Chase, led the new studies, which also included researchers from Berlin-based Metanomics Health GmbH, a company specializing in metabolic profiling. Peterson will present the new findings at the AACR Annual Meeting 2013.

"There's tremendous excitement in the cancer field for the possibility of manipulating metabolism for therapeutic benefit," Peterson says.

Patients with triple-negative breast cancer constitute about 15 to 20 percent of all breast cancer cases, though incidence is disproportionately higher among young and African-American women. In triple-negative breast cancer, tumor cells lack receptors for two hormones - progesterone and estrogen - and a protein called HER2/neu. This type of cancer is notoriously difficult to treat and does not respond to some of the most effective treatments available for other types of breast cancer, like trastuzumab, which interferes with the HER2 receptor in HER2+ breast cancer, or endocrine therapies like tamoxifen.

Triple-negative breast cancer is not one well-defined disease. It's a large group of diseases that all lack the three receptors but may differ from each other in critical ways, from individual molecules all the way up to clinical prognosis and treatment options. Peterson says that cataloging the small molecules involved in cellular metabolism may help researchers differentiate among these different cancers lacking the three receptors.

"One of our hopes is to understand how this heterogeneous disease can be classified into subtypes," says Peterson. "We'd like to be able to define each subtype and a biomarker for each of those subtypes, based on the specific metabolites altered in that subtype."

Like healthy cells, tumor cells take food from the blood and turn it into energy, but their metabolic processes differ from those of healthy cells. In recent years scientists have begun to try to find ways to exploit these differences to selectively kill cancer cells, with the ultimate goal of developing new therapies. Peterson and his colleagues used cutting edge technology, including liquid chromatography-mass spectrometry, to survey the amounts of a wide range of metabolites in cells from nine widely-used cell lines of triple-negative breast cancer. They also zoomed in to study particular, targeted metabolites more closely. Broad metabolic profiling is new technology, and Peterson and his colleagues are among the first teams of researchers to apply it to the study of triple-negative disease.