They’re investigating biological warfare with hopes of saving lives.
Researchers at the University of Virginia Cancer Center are working on turning microscopic fat balls, called lipid nanoparticles, into tiny bombs that will attach to genes of breast cancer cells to stunt their growth and thwart their expansion.
The nanoparticles would take out only the cancer cells, leaving the healthy ones to carry on.
The researchers are studying a particularly aggressive cancer known as triple-negative breast cancer. The name comes from the fact the cancer is not fueled by estrogen or progesterone or the HER2 growth-promoting protein found on the outside of all breast cells.
“It’s aggressive and it metastasizes quickly, meaning it spreads to other parts of the body, and we can’t target it with hormone therapy like other cancers,” said Sanchita Bhatnagar, a professor of biochemistry and molecular genetics at UVa School of Medicine, whose laboratory full of researchers is studying the bomb.
The effort is worthwhile. Triple-negative cells account for between 10% and 20% of breast cancers, according to the nonprofit organization Breastcancer.org. It mostly affects people younger than 50 and is more likely to be diagnosed in Black and Hispanic women.
Incidence of the disease is disproportionately higher in African American women. Their five-year survival rate is only 14% compared with 36% in non-African American women.
Because it isn’t related to a hormone, the cancer is affected little by most treatment regimens and it is resistant to chemotherapy. It accounts for an estimated 40,000 deaths each year across the country due to its chemotherapy resistance and quick growth and expansion.
“We can’t use what we have on hand for most treatments so we can’t offer many therapies for this cancer,” Bhatnagar said. “The survival rate is lower than other cancers and its rate of resistance to chemotherapy is high.”
But even a triple-negative breast cancer may have an Achilles’ Heel and Bhatnagar’s lab may have found it in a cellular gene called TRIM37, which causes the cancer to spread and is responsible for its resistance to chemotherapy.
Genes similar to TRIM37 are known as oncogenes because they often cause cancers and are found mutated in large numbers in cancer tumors. According to Breastcancer.org, most normal cells are programmed to die when their functions malfunction or their genetic codes are altered. Oncogenes, however, can cause those mutated to genes to keep on keeping on, thereby creating cancers.
“What we found was this gene is not only capable of driving the development of cancer but driving metastasis, the development of cancer in other places where the cancer hadn’t been,” Bhatnagar said.
Research by Bhatnagar’s team indicates that taking out TRIM37 in mice prevents metastatic lesions in lungs. That sparked the lab’s effort to explore how TRIM37 works and its possible role in the racial disparities of triple-negative breast cancer.
The stakes are high. Blocking the gene could benefit approximately 80% of triple-negative breast cancer patients. To develop a method, Bhatnagar joined with fellow UVa professor, researcher and spouse Jogender Tushir-Singh to develop the fat bomb.
The nanoparticles are implanted with engineered antibodies that bind to the cancerous cells, leaving healthy cells alone. After getting together with the cancer cells, the antibodies impede the cancer gene.
“Knowing the gene is like having an address and we can deliver a package to the cancer cell,” Bhatnagar said.
There is always a hitch, however. For the cancer-hunting lipids, it’s how to get them to the cells. Most nanoparticles are cleared from the bloodstream at the liver. The way around it may be up the nose and into the lungs. That’s how the lab applied the nanoparticles to mice.
“It’s at an early stage, but what we saw in mice with cancer was a significant improvement in their lungs, which is a common place for a cancer to metastasize,” she said, adding it also held true for mice that were immunocompromised.
In theory, the approach could be used on other targets besides triple-negative breast cancer. The next step is going from mice to people to test the delivery system.
“We’re talking with pharmaceutical companies and hope to develop further testing,” Bhatnagar said. “We can only do so much in the lab but it allows us to provide a proof of deliver concept. Now we have to take it out. It’s a long way from being ready, but we have to start somewhere.”