Nav: Home

How to starve triple negative breast cancer

May 13, 2019

A team of Brazilian researchers has developed a strategy that slows the growth of triple negative breast cancer cells by cutting them off from two major food sources.

Triple-negative breast cancer, or TNBC, makes up approximately 15% to 20% of all breast cancers and is most common in African American women. These tumors lack estrogen and progesterone receptors and HER2 protein which are present in other breast cancers and permit certain targeted therapies. And because every TNBC tumor has a different genetic makeup, finding new markers that could guide treatment has been a difficult task.

"There is intense interest in finding new medications that can treat this kind of breast cancer," said Sandra Martha Gomes Dias, a cancer researcher at the Brazilian Biosciences National Laboratory in Campinas, Brazil. "TNBC is considered to be more aggressive and have a poorer prognosis than other types of breast cancer, mainly because there are fewer targeted medicines that treat TNBC."

In a new study in the Journal of Biological Chemistry, Dias and colleagues demonstrate that in addition to glutamine, a well-known cancer food source, TNBC cells can use fatty acids to grow and survive. When inhibitors that block both glutamine and fatty acid metabolism were used in concert, TNBC growth and migration slowed, Dias said.

To maintain their ability to grow at a breakneck pace, cancer cells consume nutrients at an increased rate. Glutamine, which is the most abundant amino acid in plasma is one of them. Some types of cancer become heavily reliant on this versatile molecule as it offers energy, carbon, nitrogen, and antioxidant properties, all of which support tumor growth and survival, Dias said.

The drug Telaglenastat, also known as CB-839, prevents the processing of glutamine and is currently in clinical trials to treat TNBC and other tumor types. CB-839 works by deactivating the enzyme glutaminase, preventing cancer cells from breaking down and reaping the benefits of glutamine. However, recent research has shown that some TNBC cells can resist the drug treatment.

To see if alterations in gene expression could explain how these cells survive, the authors of the study exposed TNBC cells to CB-839, defined those that were resistant and those that were sensitive to the drug, and sequenced their RNA, Dias said.

In the resistant cells, molecular pathways related to the processing of lipids were highly altered, Dias said. In particular, levels of the enzymes CPT1 and CPT2, which are critical for fatty acid metabolism, were increased.

"CPT1 and 2 act as gateways for the entrance of fatty acids into mitochondria, where they will be used as fuel for energy production," Dias said. "Our hypothesis was that closing this gateway by inhibiting CPT1 in combination with glutaminase inhibition would decrease growth and migration of CB-839-resistant TNBC cells."

The double inhibition proved significant as it slowed proliferation and migration in resistant TNBC cells more than individual inhibition of either CPT1 or glutaminase. These results provide new genetic markers that could better guide drug choice in patients with TNBC, Dias said.
-end-
DOI: 10.1074/jbc.RA119.008180

This work was supported by the São Paulo Research Foundation.

Other authors on this study include Larissa Menezes dos Reis, Douglas Adamoski, Rodolpho Ornitz Oliveira Souza, Carolline Fernanda Rodrigues Ascenção, Krishina Ratna Sousa de Oliveira, Felipe Corrêa-da-Silva, Fábio Malta de Sá Patroni, Marília Meira Dias, Sílvio Roberto Consonni, Pedro Manoel Mendes de Moraes-Vieira and Ariel Mariano Silber.

About the Journal of Biological Chemistry

JBC is a weekly peer-reviewed scientific journal that publishes research "motivated by biology, enabled by chemistry" across all areas of biochemistry and molecular biology. The read the latest research in JBC, visit http://www.jbc.org/.

About the American Society for Biochemistry and Molecular Biology

The ASBMB is a nonprofit scientific and educational organization with more than 11,000 members worldwide. Most members teach and conduct research at colleges and universities. Others conduct research in government laboratories, at nonprofit research institutions and in industry. The Society publishes three journals: the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics. For more information about ASBMB, visit http://www.asbmb.org.

American Society for Biochemistry and Molecular Biology

Related Breast Cancer Articles:

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.
Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.
Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.
More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.
Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.
Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.
Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.
Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.
Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.
Does MRI plus mammography improve detection of new breast cancer after breast conservation therapy?
A new article published by JAMA Oncology compares outcomes for combined mammography and MRI or ultrasonography screenings for new breast cancers in women who have previously undergone breast conservation surgery and radiotherapy for breast cancer initially diagnosed at 50 or younger.
More Breast Cancer News and Breast Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Climate Mindset
In the past few months, human beings have come together to fight a global threat. This hour, TED speakers explore how our response can be the catalyst to fight another global crisis: climate change. Guests include political strategist Tom Rivett-Carnac, diplomat Christiana Figueres, climate justice activist Xiye Bastida, and writer, illustrator, and artist Oliver Jeffers.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Speedy Beet
There are few musical moments more well-worn than the first four notes of Beethoven's Fifth Symphony. But in this short, we find out that Beethoven might have made a last-ditch effort to keep his music from ever feeling familiar, to keep pushing his listeners to a kind of psychological limit. Big thanks to our Brooklyn Philharmonic musicians: Deborah Buck and Suzy Perelman on violin, Arash Amini on cello, and Ah Ling Neu on viola. And check out The First Four Notes, Matthew Guerrieri's book on Beethoven's Fifth. Support Radiolab today at Radiolab.org/donate.