Breast Cancer

Starving Triple Negative Breast Cancer Cells of Nutrient Kills Them

You may think of cancer cells as monsters that replicate at will. But it turns out that certain cancer cells can’t do this without a certain nutrient, and when they are deprived of this nutrient they quickly die.

This was the finding of a study that recently appeared online in Oncogene. Duke University scientists conducted the study. Their research found that triple-negative breast cancer (TNBC) cells, which are treatment resistant, die off rapidly when starved of a key nutrient called cystine.

The study

Jen-Tsan Ashley Chi, associate professor of molecular genetics and microbiology, led the study group at Duke. Earlier this year, Chi’s group published a study showing that cells from an aggressive form of kidney cancer were addicted to cystine. For this study, they wanted to see if the same was true for triple negative breast cancer cells.

In the study, both triple-negative and estrogen-positive breast cancer cells were deprived of a single key amino acid in a series of growth media. Most of the cells showed little reaction to the various amino acids used. But there was one exception — triple negative breast cancer cells died very quickly once the cystine was removed.

When searching for the cause, the study team put the cells through a battery of genetic analyses. They found that the cystine addiction is linked to a process called the epithelial to mesenchymal transition (EMT). In EMT, genetic programming allows stationary epithelial cells that are usually locked in place by certain molecules to transform into roving mesenchymal cells. This is the process that allows triple negative breast cancer cells (along with various other types of cancer cells) to break away from their neighbors and metastasize to spread throughout the body.

While this process allows these dangerous cells to effectively “cut loose” and spread the cancer throughout the body, it also opens up a pathway that requires cystine. As soon as the cystine is removed the cancer cells die.

“We found that this transition between epithelial and mesenchymal basically opens up a signaling difference that make the cells very vulnerable to cystine deprivation, leading to death,” Chi said when announcing the study results. “It is almost like EMT opens up a whole highway system (for cystine-mediated death), and therapeutically this could be very useful because there are actually compounds to block this.”

Hope for triple-negative breast cancer patients

These findings on triple negative breast cancer cells could be critical for patients with this form of breast cancer, which constitutes from 10-20 percent of all breast cancer cases. As of now, patients with triple negative breast cancer have few treatment options beyond surgery and chemotherapy. This is because triple negative breast cancer cells lack the receptors that are targeted by the most successful breast cancer therapies.

When announcing the study results, 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.

“Tumor cells use this EMT programming to move faster, to move around the body,” Chi said. “We want to take advantage of this same pathway to cure you.”

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