Newly identified gene targets could be key to preventing the spread of cancer, new University of Alberta research has shown.
In a study published last week in Nature Communications, a team of U of A researchers said that because they’ve identified the appropriate genes, there’s potential to create therapies that could almost completely block metastasis in a number of deadly cancers.
“It’s of potentially incredible significance,” said John Lewis, the Alberta Cancer Foundation Frank and Carla Sojonky Chair in Prostate Cancer Research at the U of A and a member of the Cancer Research Institute of Northern Alberta (CRINA). “Metastasis kills 90 per cent of all patients who have cancer, and with this study we have discovered 11 new ways to potentially end metastasis.”
In the study, the team used a unique platform it created—a shell-less avian embryo—to visualize the growth and spread of cancer cells in real time. The researchers used a molecular tool called a knockout library to insert short hairpin RNA (shRNA) vectors into cancer cells that bound to specific genes in the cells and stopped them from activating. They then inserted those cancer cells into the shell-less embryos and observed as they formed clusters of cancer, identifying which ones showed properties of being non-metastatic.
“When we found compact colonies [of cancer], that meant that the key steps of metastasis were blocked,” said Konstantin Stoletov, lead author of the study and a research associate in the Lewis lab. “After that we could pull them out, query what the gene is and then validate that the gene is actually responsible for metastasis.”
The approach allowed the team to detect and identify 11 genes that play essential roles in cancer cell metastasis. According to the researchers, the genes discovered are widely involved in the process of metastasis and not unique to any one cancer.
They now plan to test the metastasis-associated genes and gene-products as drug targets with an aim of stopping metastasis.
“We know that cancer, once it becomes metastatic, will keep spreading to other parts of the body and continue to get worse because of that,” said Lewis. “If we can stop metastasis at any step of progression in cancer patients, we’re going to have a significant effect on survival.”
The team is now hoping to progress its research to human trials over the next few years. The Lewis lab is also expanding efforts to explore for other types of genes called microRNAs that may present even stronger therapeutic targets for preventing metastasis.
The research was funded by the Canadian Cancer Society and the Alberta Cancer Foundation.
Lewis and Stoletov’s paper, “Quantitative in vivo whole genome motility screen reveals novel therapeutic targets to block cancer metastasis,” was published June 14 in Nature Communications.
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