The End Of Chemotherapy?

Exciting new research from Northwestern Medicine has discovered that inside every cell within the human body is a toxic kill code designed to trigger self-destruction if it senses a cell is turning cancerous. Across two newly published studies, the scientists remarkably homed in on the exact nucleotide code underlying this mechanism and believe it may lead to an entirely novel kind of cancer treatment. The research originally started with Marcus Peter and his team at Northwestern wondering what natural mechanisms could have developed to protect multicellular organisms from cancer before the adaptive immune system evolved. Last year, the breakthrough research first revealed a powerful ancient kill switch in the human genome that can trigger small RNA molecules (called siRNAs). These tiny assassin molecules, which are also triggered by chemotherapy, are incredibly effective at targeting and destroying cancer cells, yet the exact mechanism by which they killed the cancer cells was unclear.

The new research began with the knowledge that what helped the siRNAs destroy cancer cells was a single sequence of six nucleotides, called 6mers. There are 4,096 different possible combinations of nucleotides in the 6mers, and the researchers tested each one until they discovered the combination most toxic to cancer cells. The most toxic 6mer combination was dubbed G-rich, and excitingly the researchers discovered this same 6mer was utilised by microRNAs the body naturally releases to battle cancerous cells. A second newly published study by the researchers dug down even further into the mechanism that induces cancer cell death to reveal new and exceptionally detailed insight into how this natural process can effectively kill cancer. Peter suggests that cancer cells can never develop a resistance to this destructive mechanism, as it attacks cancer from multiple angles simultaneously. “It’s like committing suicide by stabbing yourself, shooting yourself and jumping off a building all at the same time. You cannot survive,” says Peter.

The implications of this research are undoubtedly massive, although at this stage any actual human therapy is a long way off. The plan, now the researchers have decoded the exact mechanism that can destroy cancer cells, is to design artificial microRNAs that are even more effective than the natural molecules. “Now that we know the kill code, we can trigger the mechanism without having to use chemotherapy and without messing with the genome,” says Peter. “We can use these small RNAs directly, introduce them into cells and trigger the kill switch.” Perhaps the most exciting aspect of this research is the way it harnesses ancient mechanisms that nature developed over millions of years of evolution. It’s estimated that this cancer-killing siRNA mechanism arose over 800 million years ago, and now humans have discovered it, hopefully, we can improve on it to develop effective cancer treatments.

The two new papers were published in eLife and Nature Communications.

Credit: Rich Haridy for New Atlas, 31 October 2018. Source: Northwestern University.