Novartis, Broad researchers find hope in potential gene target for intractable cancers
- Cancer researchers at the Novartis Institutes for BioMedical Research (NIBR) and the Broad Institute may have identified a new target to treat intractable cancers such as gliobastoma brain cancer or pancreatic cancer.
- The research, published in Science on February 11, zeroes in on a gene known as PRMT5. In a test of 390 cancer cell lines, researchers discovered that preventing the expression of PRMT5 led to the death of cancer cells missing a major tumor suppressor.
- Cancers missing tumor suppressors—one of the body's natural defenses against cancer growth—are often difficult to treat. While this research is still in its early stages, it could be a foundation for future treatments.
In healthy cells, tumor suppression genes normally work to check tumor growth. However, the mutation or deletion of these cells can lead to rapid cancer growth. Researchers at NIBR and the Broad Institute examined the common tumor suppressor CDKN2A, which is missing in 30% of known cancer cells.
Many cancer cells missing CDKN2A are also missing another metabolic enzyme known as MTAP. The deletion of MTAP in cancer cells leads to a toxic buildup, subsequently causing a drop in PRMT5 activity vital to the cell's functioning. When the scientists further suppressed PRMT5, the cancer cells promptly died.
"These cancers, for whatever reason, were exquisitely dependent on PRMT5 activity for survival," said author and NIBR researcher Konstantinos Mavakis in an NIBR blog.
This result is encouraging because cells missing both CDKN2A and MTAP are frequently associated with difficult to treat tumors. By identifying a major weakness in these cancerous cells, the researchers may have discovered a new way to treat the cancers. However, PRMT5 is an essential gene for normal cells as well. Any future treatment would have to exclusively target PRMT5 in cancerous cells while leaving normal cells' PRMT5 genes untouched.
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- Boston Globe Targeting the ‘gene next door’ to fight hard-to-treat tumors
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