A new therapy targeting genomic rearrangements, such as fused genes that promote tumor development, significantly improved survival in mice with aggressive forms of prostate and liver cancer.
The study, “Targeting genomic rearrangements in tumor cells through Cas9-mediated insertion of a suicide gene,” was published in the journal Nature Biotechnology.
“This is the first time that gene editing has been used to specifically target cancer fusion genes. It is really exciting because it lays the groundwork for what could become a totally new approach to treating cancer,” the study’s lead author, Dr. Jian-Hua Luo, said in a press release. The pathology professor directs the High Throughput Genome Center at the University of Pittsburgh School of Medicine.
Fusion genes occur when two genes, which normally are separated, fuse to create an abnormal gene with altered functions. Fusion genes are often associated with cancer, but targeting them to develop a cancer treatment has been difficult.
In a previous study, Luo and his team identified a set of fusion genes that promote recurrent and aggressive prostate cancer. The MAN2A1-FER gene, which promotes cancer progression and invasiveness, is also present in other cancers, including those of the liver, lungs and ovaries.
Using CRISPR-Cas9 genome editing technology, researchers targeted DNA sequences in a fused gene that was in prostate and liver cancer cells. They used viruses to deliver the genome editing tools to the cells. The editing process involved replacing the fused DNA with a gene that could trigger the death of the cancer cell.
They edited only cancer cells for death, leaving healthy cells unharmed. That targeting would be crucial to doctors being able to use editing to treat cancer patients.
To see if editing can be used as a cancer treatment, the scientists inserted genomic-edited cells into mice, then tracked the animals’ tumor growth for three weeks. The team delivered viruses with no edited genes to mice that constituted a control group.
The tumor size of mice with edited cancer fusion-genes shrank by 30% during the eight weeks, researchers said. The mice also remained free of metastasis, or the spread of cancer to other locations, the team said.
Meanwhile, the tumors in the control group grew by 40%. And all of the control mice developed metastasis and died by the end of the study.
Overall, the findings support the idea of genome editing as a new cancer strategy, the team said.
“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,” Luo said.
The strategy also allows researchers to target genomic mechanisms that cancer cells use to become resistant to standard therapies like chemotherapy. This includes the cells’ acquisition of new mutations.
Researchers plan further studies to if genome editing can eradicate cancer, rather than just induce remission.