Scientists from the Australian National University (ANU) and the Peter MacCallum Cancer Center have discovered that a protein, called Menin, contributes to the abnormal deactivation of specific genes in cancer cells.
One of the hallmarks of cancer is that normal gene regulation is disrupted, and this causes cancer cells to look and behave differently from normal cells. Cancer cells can turn off certain genes, keeping them in a dormant state. By turning off specific immune genes, some cancers can evade detection by the immune system, essentially becoming invisible. This allows the cancer to grow and become more aggressive.
By targeting the Menin protein with drug therapies, researchers believe they can reactivate these genes, making cancer cells visible again and allowing the immune system to seek them out and destroy them.
The findings, published in Nature Cell Biology, could lead to new and more effective treatments for lymphoma and lung cancer.
Professor Mark Dawson, from the Peter MacCallum Cancer Centre, said the findings help scientists learn more about how cells work.
Our research discovery has important implications for many different fields of research because we need to understand how cells make decisions and change the way they act to find new ways to treat cancer.”
Professor Mark Dawson, Peter MacCallum Cancer Centre
ANU Associate Professor Marian Burr, who is one of nine Snow Fellow researchers across the country and joint lead author, said the researchers used gene-editing technology to remove the Menin protein from the cells. cancer cells
“Menin has previously been shown to activate genes. However, our research unexpectedly found that menin works to keep these genes in a dormant, inactive state,” Associate Professor Burr said.
“This meant that by deleting Menin we could activate immune genes, which is essential for helping the immune system detect and kill cancer cells.
“Importantly, specific drugs that inhibit Menin have been developed and are currently being tested in clinical trials for specific forms of leukemia.
“Our findings expand the potential clinical uses of these drugs. We have shown that menin inhibitors can be used in combination with other existing treatments to enhance the destruction of lymphoma and lung cancer cells in the laboratory.
“We think these drugs could also be effective in other types of cancer.”
Source:
Australian National University
Journal reference:
Sparbier, CE, et al. (2023) Menin targeting alters KMT2A/B and polycomb balance to paradoxically activate bivalent genes. Nature Cell Biology. doi.org/10.1038/s41556-022-01056-x.