A team of US researchers, led by professor Jason Moffat from the University of Toronto‘s Donnelly Centre, is ushering in a new breakthrough in understanding how our genome works and which genes are crucial in diseases like cancer.
Moffat’s team has switched off, by turn, almost 18,000 genes – 90% of the entire human genome – in five cancer cell lines (including brain, retinal, ovarian and colorectal), which revealed a core set of more than 1,500 essential genes that each cell line relies on for survival.
This raises the possibility of devising new treatments that would target only cancer cells, leaving the healthy tissue unharmed.
Since the time when sequencing of the human genome was completed 12 years ago, resulting in the identification of 20,000 genes, scientists have been trying to understand their function by turning them off and on one by one.
At first, the process was either inaccurate or too slow, but with the advent of the gene-editing technology CRISPR, which made things much faster and more precise, a global race among multiple competing research teams was kicked off.
Along with a paper from Harvard and MIT, published recently in Science, the Toronto study has shown that roughly 10% of our genes are essential for cell survival.
What the researchers found was that the function of these core genes is more subtle than might otherwise be expected – while turning off one or two does not necessarily lead to pathology, when more of them are mutated at the same time, or the cells are under environmental stress, things could turn for the worse.
And since each line of cancer cells depends on a different set of “trigger genes”, devising drugs that target only those genes could change the game of cancer treatment in extraordinary ways.
“We can now interrogate our genome at unprecedented resolution in human cells that we grow in the lab with incredible speed and accuracy. In short order, this will lead to a functional map of cancer that will link drug targets to DNA sequence variation,” noted Moffat.
The team has already demonstrated that this could work by successfully killing brain cancer cells with a diabetes medication Metformin, and colorectal cancer cell with antibiotics chloramphenicol and linezolid.
“The Moffat group has developed a powerful CRISPR library that could be used by investigators around the world to identify new treatment strategies for the treatment of cancer,” said Dr. Aaron Schimmer of the Princess Margaret Cancer Centre in Toronto, who was not involved in the study.