Researchers at the University of North Carolina's School of Medicine have discovered why some of the most aggressive and fatal breast cancer cells are resistant to chemotherapy.
The protein Engrailed 1 is "overexpressed" in basal-like carcinomas and researchers hope to shut down the protein and kill the basal-like tumors with a chain of amino acids they're designing.
"Patients with basal-like breast cancer tend to initially respond well to chemotherapy, but it's common for patients to relapse even more aggressively," Adriana S. Beltran, PhD, a research assistant professor in the department of pharmacology, said in a statement. "We believe that relapse is caused by a small number of cancer cells that have stem cell properties that allow them to survive chemotherapy. In these cells we've identified the overexpression of Engrailed 1."
Beltran and her researchers found Engrailed 1 is not involved in the rapid proliferation of cells that cause tumor growth. Nor is Engrailed 1 present in luminal tumors - the most common form of breast cancer. The protein only appears in basal-like breast cancer.
According to a press release, the protein is normally confined to the brain, where it protects neurons from cell death and helps maintain their normal activity. Parkinson disease is what results when the Engrailed 1 protein is absent from the brain. There's no known function of Engrailed 1 within breast tissue.
"We think that Engrailed 1 confers protective features to breast cancer cells, similar to the features observed in long-lived neurons," Beltran said. "This may explain why these cells survive and become resistant to chemotherapy in our experiments."
Although, the reason why Engrailed 1 is manifested in cancerous breast tissue remains a mystery, researchers think they may have found a way to stifle it. Researchers created a synthetic peptide - a chain of amino acids - that can suppress the binding power of Engrailed 1. In cell lines - not in animals or patients - Beltran and colleagues used their peptide to disrupt Engrailed 1 from binding to its protein partners and DNA.
"Cancer cells need Engrailed 1 to live," Beltran said. "The peptide abolishes all interactions of Engrailed 1, and as a consequence Engrailed 1 cannot perform its functions, causing rapid cell death of the cancer cell."
The research team's goal is to see if these amino acids can work in animal models. The findings could result in a drug could being developed to fight cancer relapse in some of most deadly forms of breast cancer, according to the researchers.
