Scientists are closing in on the goal of finding drugs to target genes that drive individual cancers while leaving healthy tissue unharmed. Taking a significant step in this direction, a study published in Cell describes how one team has mapped over 1,500 genes that are essential for cancer cell survival.
The researchers, from the University of Toronto in Canada, have also found subsets of genes unique to some individual cancers and identified drugs that target them.
In 2003, the Human Genome Project published the first map of the 20,500 genes of the human genome – the equivalent of a parts list for making our cells and bodies.
Since then, scientists have been trying to study the genes to find out what they do and how they influence health and disease.
But they soon discovered this would be a lengthy, laborious task, involving switching genes off one by one across the whole genome to find out which cell processes go wrong in each case. And it did not help that the tools they had were slow and not accurate enough to locate individual genes.
Then, about 3 years ago, the arrival of the Swiss army knife of genome-editing – a technology called CRISPR – galvanized a global race among scientists as they realized they could quickly pinpoint and switch genes off in the genome.
For the new study, the researchers used CRISPR to turn off, one by one, nearly 18,000 genes – that is, 90% of the human genome – to identify the “core” 1,500 that are essential for cell survival.
Also, by turning genes off in different types of cancer cell – such as from brain, retinal, ovarian and colorectal cancers – the team found each tumor is driven by a unique cluster of genes that could potentially form the target of specific drugs.
The achievement is a significant step toward personalized medicine with drugs that target only cancer cells without harming healthy cells, as senior author Jason Moffat, a professor researching the genetics of cancer at the University of Toronto’s Donnelly Centre, explains:
“It’s when you get outside the core set of essential genes, that it starts to get interesting in terms of how to target particular genes in different cancers and other disease states.”
Evidence from this study and a paper by researchers from Harvard University and Massachusetts Institute of Technology (MIT), recently published in the journal Science, suggest around 10% of our genes are essential for cell survival.
This means that for the vast majority of genes, switching off a gene does not disrupt a cell so much that it dies. However, if this event is combined with another – such as environmental stress or the silencing of another gene – then it starts to have an effect.
“We can now interrogate our genome at unprecedented resolution in human cells that we grow in the lab with incredible speed and accuracy,” explains Prof. Moffat, who says he sees it leading to a “functional map of cancer that will link drug targets to DNA sequence variation.”
The team has already identified some drugs that can potentially target unique clusters of genes essential for cell survival in some individual cancers.
In their paper, they describe how metformin – a drug commonly used in the treatment of diabetes – successfully killed brain cancer cells and cells from one type of colorectal cancer, but did not work against the other cancers they studied.
But cells of another type of colorectal cancer they studied did succumb to the antibiotics chloramphenicol and linezolid, which had no effect on the other cancer types.
Aaron Schimmer, a professor whose lab at the University of Toronto searches for new ways to target leukemia and leukemia stem cells, and who was not involved in the study, says the team has produced a “powerful CRISPR library” that researchers around the world can use to find new ways to treat cancer, and adds:
“I would be interested in using this tool to identify new treatment approaches for acute myeloid leukemia – a blood cancer with a high mortality rate.”
Meanwhile, Medical News Today recently learned how another group of researchers is working on an intelligent biogel that kills cancer tumors. When injected into a tumor, the gel releases a deadly payload of anti-cancer immune cells.