In a study recently published online on Nature Biotechnology, University of Pittsburgh School of Medicine researchers report that a new technique using the CRISPR-Cas9 genome editing technology effectively targets cancer-causing “fusion genes” and improves survival in mouse models of aggressive liver and prostate cancers.
Professor of pathology at Pittsburgh’s School of Medicine, Jian-Hua Luo, M.D., Ph.D., explains that this is the first time that gene editing has been used to specifically target cancer fusion genes. The professor also adds that this is “really exciting” because it paves the way for what could become an entirely new approach to cancer treatment.
Fusion genes are hybrid genes formed from two previously separate genes. This ‘fusion’ can occur as a result of gene translocation, interstitial deletion, or chromosomal inversion, and produce abnormal proteins that can cause or accelerate cancer growth. In short, these fusion genes are often associated with cancer.
A panel of fusion genes responsible for recurrent and aggressive prostate cancer has been previously identified by Dr. Luo and his team. Earlier this year, in a study published on Gastroenterology, they described how one of these fusion genes, known as MAN2A1-FER, can be found in other types of cancer, such as that of the lungs, ovaries, liver, and is also responsible for rapid tumor growth and invasiveness.
As described in a press release, for this study, the team used CRISPR-Cas9 to target unique DNA sequences formed as a result of fusion genes. The process involves the use of viruses to deliver gene editing tools that remove the mutated DNA of the fusion gene, then replacing it with genes that cause cancer cells to die.
Because fusion genes are only present in cancer cells and not healthy cells, the gene therapy is quite specific. In contrast with present cancer treatments such as chemotherapy which indiscriminately attacks both cancerous and healthy cells, this new approach will be much more preferable because it only attacks cancerous cells and leaves healthy cells intact.
To conduct the study, the team used mouse models which received transplants of human prostate and liver cancer cells. This group of mice was treated with the CRISPR gene editing tool. After the 8-week treatment period, their tumors shrunk by up to 30%, did not spread throughout their bodies, and all of them survived.
On the other hand, in a control group which was treated with viruses that target a kind of fusion gene that wasn’t present in tumors, the results were a stark contrast. The mice had tumors growing almost forty times bigger. And in most cases, the tumors spread to other parts of their bodies. Most importantly, none among the group survived.
The findings suggest a new and different way to attack cancer. As Dr. Luo explained, “Other types of cancer treatments target the foot soldiers of the army. Our approach is to target the command center, so there is no chance for the enemy’s soldiers to regroup in the battlefield for a comeback.”
Dr. Luo also notes that another advantage of their approach over existing cancer treatments is that it is highly adaptive, not to mention target-specific. Going forward, they plan to test whether their strategy can do more than just stop or delay the spread of the disease. The aim of course, is to hopefully one day completely eradicate it.