Photo of Gene-editing finds vulnerabilities in cancer cells

Gene-editing finds vulnerabilities in cancer cells

by Lindsay Jolivet Genetic Networks News 03.02.2016

Researchers have exposed the weak points of several types of cancer using a gene-editing technique that can turn genes on and off with pin-point accuracy.

CIFAR fellows Jason Moffat, Frederick P. Roth (both University of Toronto) and their collaborators used the gene editing technology CRISPR-Cas9 to turn off  approximately 18,000 genes in human cancer cells, one at a time. They were trying to uncover more of the set of genes that are essential for cells to survive, and found that about 10 per cent of human genes are essential.

This set of “core essential genes” is important in both healthy cells and cancerous cells. But the researchers were also interested in genes that become important in certain situations or “contexts”. For example, if a genetic mutation causes breast cancer, other genes may become needed for the cancerous cells to multiply. The researchers use the image of a daisy, with the core representing the essential genes.

“There is a core set across pretty much every different context that you can imagine,” Moffat says. The petals, on the other hand, may overlap in function or not be involved in every process inside the cell at all times, but they are all connected at the core.

The researchers studied tumours from brain cancer, two types of colorectal cancer, skin cancer and ovarian cancer, as well as non-cancerous retinal cells, and identified genes that are important for cells in each type. Knowing which genes a cancer cell needs to survive, but that a healthy cell can do without, creates the opportunity to choose drugs that target those cancer-helping genes.

It could also be a huge boon to personalized medicine. Moffat uses the example of a patient being diagnosed with cancer and then receiving their tumour’s genetic sequence, which he says could be standard in the near future. Knowing the precise genetic makeup of that tumour could help doctors match patients with the treatment that will be most likely to kill their cancer.

“Our next big hurdle is to develop a comprehensive toolkit of drugs to be able to use against all these genetic backgrounds in tumours,” Moffat says. The study identified a few drugs and combinations of drugs that could effectively target certain cancer types.

Moffat says the research would not have been feasible without CRISPR, which has made it significantly faster to edit the genome over the past few years. CRISPR is a tool that bacteria use to build immunity against viruses by saving snippets of DNA and incorporating it into its own genome. Scientists discovered CRISPR in bacteria and harnessed the ability to cut and insert genetic material into genomes, vastly increasing the speed and accuracy of DNA research.

The findings bring us closer to understanding the purpose of each gene in the human genome, which is a main goal of CIFAR’s program in Genetic Networks.

“It’s sets the stage for us to be able to build the first robust genetic interaction network in human cells,” Moffat says. “The technology is enough that we don’t need to wait. We just need to move forward.”

The research was published in Cell and covered widely by media including the Atlantic, Maclean’s and Motherboard.

Image above: 3D structure of a melanoma cell. Credit: Sriram Subramaniam, National Cancer Institute, National Institutes of Health

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