Discovery of cancer ‘kill code’ could inspire new treatments

Scientists at Northwestern University have discovered a "kill code" in every cell of the body that’s triggered by chemotherapy and that causes cancerous cells to self-destruct. What’s more, they’ve learned enough about the code that they’ve figured out how to trigger it without chemo—a finding that they believe could lead to new therapies.

The discovery, reported in the journals Nature Communications and eLife, is a code that’s found in both large and small ribonucleic acids (RNAs). The researchers also have early evidence that the small RNAs, called microRNAs, can be introduced into cells to trigger the kill switch.

"My goal was not to come up with a new artificial toxic substance," said lead author Marcus Peter, Ph.D., a professor of cancer metabolism at Northwestern’s Feinberg School of Medicine, in a statement. "I wanted to follow nature's lead. I want to utilize a mechanism that nature developed."

In research Peter published last year, he showed that cancer cells treated with toxic RNA molecules don’t become resistant, because genes that the cells need to survive also die. In this most recent study, he was able to determine the mechanism that causes the cells to self-destruct.

That mechanism involves six nucleotides in small RNAs. Peter’s team tested 4,096 combinations of nucleotide bases in those RNAs and hit on one that seems to be the most toxic to cancer cells. Separately, they discovered that a gene that promotes the growth of cancer cells gets chopped into pieces that act like cancer-killing microRNAs.

Although much of the excitement in oncology research of late has focused on immunotherapy, there is still significant interest in improving chemotherapy—or replacing it with drugs that confer its benefits without its harmful side effects. Startup Ascentage, for example, recently raised $150 million to advance its pipeline of drugs that work by promoting apoptosis, or programmed cell death, in cancer cells.

Academic researchers are investigating a variety of approaches for tricking cancer cells into self-destructing. A team at Brigham and Women's Hospital is using the gene-editing technology CRISPR to give cancer cells the ability to recognize and kill other cancer cells. Researchers at Mount Sinai School of Medicine also used CRISPR to discover one mechanism that causes melanoma cells to become resistant to BRAF inhibitors—a finding that led them to a drug combination that may boost apoptosis in cancer cells and reduce resistance.

Northwestern’s Peter believes his team’s findings could be used to develop cancer treatments that mimic the newly discovered toxic microRNAs. "Based on what we have learned in these two studies, we can now design artificial microRNAs that are much more powerful in killing cancer cells than even the ones developed by nature," Peter said.

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