Two recent studies detail a natural mechanism that, if harnessed properly, can kill cancer cells and their ability to become resistant to treatment without the side effects of chemotherapy.
In a study published last year, scientists led by Marcus E. Peter and Tomas D. Spies from Northwestern University Feinberg School of Medicine in Chicago (USA) revealed not only that certain RNA molecules can kill cells cancerous, but can also simultaneously prevent them from becoming resistant to treatment.
As the experts explained at the time, RNA molecules destroyed cancer cells, but they also eradicated various genes that cancer cells needed to survive. “It’s like committing suicide by stabbing, shooting, and jumping off a building at the same time. You can’t survive,” explained Marcus E. Peter.
However, the exact mechanism that caused cancer cells to “commit suicide” remained unknown, until now.
Two new studies, led by Peter, have discovered a code that is embedded in the RNA and microRNAs of each individual cell. The mechanism may be responsible for the self-destructive capacity of cancer cells.
The first of the two studies, published in the journal eLIfe, details how large RNAs can be transformed into small, toxic RNAs.
The second study, which describes how these small microRNA molecules use the “death code” to destroy cancer cells, was published in the journal Nature Communications.
Flipping the kill switch
In previous research, the experts found a sequence of six nucleotides contained in small RNAs that made these molecules toxic to cancer cells. A nucleotide is the basic structural unit and building block for DNA and RNA.
In the first of the current studies, the authors found that about 3% of all large RNAs can be “cut” into small pieces that then act as toxic microRNAs that can kill cancer.
In the second study, the researchers tested nearly 4,100 different nucleotide base combinations from those initial six nucleotides in an attempt to find the most lethal and toxic combination.
“Based on what we have learned from these two studies, we can now design artificial microRNAs to kill cancer cells that are much more powerful than even those developed by nature,” explains Peter. “We need to turn this into a novel form of therapy .”
And without chemo
“Now that we know the elimination code, we can activate the mechanism without having to use chemotherapy and without altering the genome. We can use these small RNAs directly, introduce them into cells,” the expert clarifies.
“My goal was not to create a new artificial toxic substance. I wanted to follow the example of nature. I want to use a mechanism developed by nature,” Peter ends.
Because cancer cannot adapt to toxic RNAs, the findings could one day lead to unstoppable cancer treatment. However, the researcher cautions that many years may pass before such treatment is a reality.
Reference: CD95 / Fas ligand mRNA is toxic to cells. Will Putzbach, Ashley Haluck-Kangas, Quan Q Gao, Aishe A Sarshad, Elizabeth T Bartom, Austin Stults, Abdul S Qadir, Markus Hafner, Marcus E Peter. eLife 2018; 7: e38621 doi: 10.7554 / eLife.38621 // 6mer seed toxicity in tumor suppressive microRNAs. Quan Q. Gao, William E. Putzbach, Andrea E. Murmann, Siquan Chen, Aishe A. Sarshad, Johannes M. Peter, Elizabeth T. Bartom, Markus Hafner & Marcus E. Peter. Nature Communications volume 9, Article number: 4504 (2018) DOI_: https://doi.org/10.1038/s41467-018-06526-1
