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| Triple negative breast cancer cells died rapidly when deprived of cystine |
CANCER DIGEST – Nov. 27, 2016 – In a new study, Duke University scientists report that an aggressive and treatment-resistant form of breast cancer, called triple negative breast cancer (TNBC), die off rapidly when deprived of a key nutrient called cystine.
Patients diagnosed with triple negative breast cancer, which constitute about 10 to 20 percent of all breast cancer cases, have few treatment options outside of surgery and chemotherapy.
That is because the most successful breast cancer therapies target two of three receptors commonly found in tumor cells – estrogen receptor, progesterone receptor, or the Her2/neu receptor -- but triple negative breast cancer cells lack all three.
That is because the most successful breast cancer therapies target two of three receptors commonly found in tumor cells – estrogen receptor, progesterone receptor, or the Her2/neu receptor -- but triple negative breast cancer cells lack all three.
In the Duke study led by Jen-Tsan Ashley Chi, associate professor of molecular genetics and microbiology at the Duke University School of Medicine, results indicate that blocking cystine uptake may be an effective way of treating not only triple negative breast cancer, but other aggressive cancers that use this pathway during metastasis. The study appeared online Nov. 21 in Oncogene.
Some earlier studies, including one by Chi’s group in kidney cancer, have suggested that certain aggressive cancer cells cannot survive without cystine. To find out if this was also true for triple negative breast cancer, Xiaohu Tang, a postdoctoral fellow in Chi lab, submitted both triple-negative and estrogen-positive breast cancer cells to a nutrient deprivation test: growing batches of each cell type in a series of different growth media, each missing just one out of 15 key amino acids.
Most of the cells showed little reaction to these small changes in diet, Chi said. But there was one notable exception, those deprived of cystine died rapidly. In addition, they found that cystine addiction is linked to a process called the epithelial to mesenchymal transition (EMT), a bit of genetic programming that allows stationary epithelial cells, to break away from the primary tumor and metastasize.
"The triple negative breast cancer cells were very sensitive to cystine," Chi said. "So if you removed cystine, they just rapidly died, while the other breast cancer cells didn't care."
Chi says the team is now in the process of testing out cystine-blocking molecules on tumors and searching for biomarkers that will help identify when cancers are likely to respond positively to this treatment.
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