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

April 9, 2013

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 ," 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 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 , which interferes with the 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 involved in may help researchers differentiate among these different cancers lacking the three receptors.

"One of our hopes is to understand how this 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, 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.

They looked at both the metabolic "footprints" and "fingerprints" of the cells. The metabolic "footprint" includes the metabolites that go in to a cell from the surrounding media—or come out the other end of the process. The metabolic "fingerprint" shows all the molecules that work inside the cell during metabolic processes.

"We basically remove all the cells from the media, and then extract all of their small metabolites(less than 1500 dalton) and analyze those," Peterson says.

He says this catalog of metabolites from these cell lines is a good first step toward using metabolic markers to better understand the disease. Since triple-negative breast cancer is heterogeneous, the next step, he says, is to replicate the study in other cell lines and validate potential biomarkers.

This study grew out of another ongoing project by Peterson and his team. He was the lead author on a paper, published in the journal Nature Biotechnology in 2011, introducing a new technique to study the action of kinases—which are a class of enzymes that control cellular metabolism. Once that tool was developed, he decided to apply it to the poorly understood triple-negative . In another study he's presenting at the AACR Annual Meeting 2013, Peterson and colleagues show how this technique can be used to identify small molecules that block the kinases important to the growth of triple-negative disease.

"Those small molecules may be the starting point for new therapies," he says. Ultimately, he says, he'd like to combine the metabolite and kinase studies to develop targeted therapies that stymy the metabolism of cancer cells.

Explore further: Omega-3 fatty acids more effective at inhibiting growth of triple-negative breast cancer

Related Stories

Omega-3 fatty acids more effective at inhibiting growth of triple-negative breast cancer

April 9, 2013
Researchers from Fox Chase Cancer Center have found that omega-3 fatty acids and their metabolite products slow or stop the proliferation, or growth in the number of cells, of triple-negative breast cancer cells more effectively ...

Drug shows promise for triple-negative breast cancer

July 3, 2012
(Medical Xpress) -- A promising new therapy for hard-to-treat triple-negative breast cancer has been reported in the journal Breast Cancer Research by a team at the Tulane University School of Medicine, led by Dr. Bridgette ...

Paragazole excels in preclinical models of triple-negative breast cancer

April 8, 2013
Breast cancers that lack estrogen receptors are more difficult to treat than ER+ cancers. Research presented at the AACR Annual Meeting 2013 demonstrates an investigational drug, Paragazole, that makes triple-negative breast ...

Researchers discover biological diversity in triple-negative breast cancer

February 13, 2013
Triple-negative breast cancers are more biologically diverse than previously believed and classification should be expanded to reflect this heterogeneity, according to University of North Carolina researchers.

A form of small pox virus shows potential for treating triple-negative breast cancer

October 1, 2012
Researchers from Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City have shown that a new vaccinia virus, acting as both an oncolytic and anti-angiogenic agent, can enter and kill triple-negative breast cancer ...

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.