Canadian researchers have identified key therapeutic targets that could stop the spread of cancer. They found that by inhibiting several newly identified gene targets they could block more than 99.5 percent of cancer metastasis in living cells.
The team led by John Lewis, a professor at the University of Alberta, used a shell-less avian embryo to visualize the growth and spread of cancer cells in real time. When they inserted short hairpin RNA (shRNA) vectors into the embryo, the vectors bonded to specific genes in the cancer cells, thereby stopping them from activating. The researchers then inserted the modified cancer cells into a shell-less embryo, allowing them to see which ones were non-metastatic.
"When we found compact colonies [of cancer], that meant all the steps to 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.
This unique approach allowed the researchers to identify 11 genes that seem to be key in cancer cell metastasis.
Metastasis is when a secondary malignant growth occurs away from the original cancer. Bearing this in mind, blocking metastasis won't "cure" the original cancer -- it will, however, greatly improve the survival odds of patients undergoing surgery or chemotherapy.
"Metastasis kills 90 percent of all patients with cancer. With this study we have discovered 11 new ways to potentially end metastasis," Lewis said.
In the future, the team plans on targeting these metastasis-associated genes with drugs that might stop the metastasis. Human trials might begin in a few years, researchers hope.
"We know that cancer, once it becomes metastatic, will continue to seed other parts of the body and the disease will progress and get worse because of that," said Lewis. "So I think if we can stop metastasis at any step of progression in cancer patients, we're going to have a significant effect on survival."
Lewis also plans on exploring other targets. He has his eyes set on other types of genes called microRNA that have the potential to be even stronger therapeutic targets.
Scientific reference: Konstantin Stoletov, Lian Willetts, Robert J. Paproski, David J. Bond, Srijan Raha, Juan Jovel, Benjamin Adam, Amy E. Robertson, Francis Wong, Emma Woolner, Deborah L. Sosnowski, Tarek A. Bismar, Gane Ka-Shu Wong, Andries Zijlstra, John D. Lewis. Quantitative in vivo whole genome motility screen reveals novel therapeutic targets to block cancer metastasis. Nature Communications, 2018; 9 (1) DOI: 10.1038/s41467-018-04743-2.
