When missing segments of the genome matter in cancer, it's bad news because those deletions have wiped out a gene that blocks or hinders cancer formation and growth.
But now scientists have found genomic deletions that expose weaknesses to exploit in malignant cells. These deletions occur as collateral damage to neighboring genes when tumor-suppressors are destroyed.
This week in Nature, Florian Muller, Ph.D., instructor in MD Anderson's Department of Genomic Medicine, and colleagues demonstrate how to identify and attack these vulnerabilities.
Working in cell lines and mouse models of glioblastoma multiforme, the most lethal form of brain tumor, the team discovered that when collateral damage erases a "housekeeping" gene that is vital to cell survival, cancer cells can be killed by blocking another gene that does the same job.
"In this case, we looked at passenger deletions - genes co-deleted along with tumor-suppressor genes, but not directly involved in cancer promotion - as a starting point for identifying potential targets and therapies," Muller said.
Most cancer research focuses on understanding and attacking active cancer-driving genes that are amplified or dysfunctional due to genetic mutations. Efforts to counter driver deletions of tumor-suppressors have yet to show promising results.
Innovative way to develop targeted therapies
The team identified a gene called ENO1 that is deleted in about 5% of glioblastoma cases on part of chromosome one that harbors candidate tumor-suppressing genes. When the scientists inhibited activity of ENO2, a gene on chromosome seven that backs up ENO1, they killed glioblastoma cells.
