Researchers have discovered a vulnerability in lymphomas that could change the way oncologists target cancers that begin in the infection-fighting cells of the immune system.
OK, some Science 101: Cancer cells often rely on a single gene – the “driver oncogene” – and need it for survival. By targeting this driver oncogene, oncologists can extend the cancer patient’s life.
MYC is a proto-oncogene that encodes the proteins found in the nucleus of a cell and is part of cell cycle progression, apoptosis, and cellular transformation. (Basically, MYC helps cells do their thing and eventually die as a regular part of our growth or development.) MYC also fuels blood cancers such as lymphoma and leukemia.
But therapies cannot target MYC; it’s necessary for all cells – not just cancer cells. So, how can we target what makes a cell malignant? Researchers developed an in vivo model of MYC-addicted T cell acute lymphoblastic leukemia within mice. The study showed cancer regression after turning off MYC. Hence, their goal was to identify immune compartments and processes that generate immunological memory.
Walter and Eliza Hall Institute researchers note to 70% of human cancers – including many blood cancers – have high levels of MYC, which forces cells into abnormally fast growth. The study revealed that MYC-driven lymphoma cells rely on the protein MNT for survival, and without it, the cells die. The findings suggest that inhibiting MNT is worth further study as a new approach to treat MYC-driven cancers.
The institute’s study results were published in the journal Blood. [1]
Prof. Suzanne Cory, who has studied MYC-driven cancers for more than 30 years, said, “For many years we hoped for a drug that could directly target MYC as a potential cancer treatment,” but those inhibitors have failed to deliver overarching results. “It became clear we needed to look for other vulnerabilities in MYC-driven cancers,” she said. [2]
By deleting the gene encoding MNT from MYC-driven lymphocytes – the immune cells from which lymphomas begin – the researchers learned that MNT plays an essential role during MYC-driven lymphoma.
“That role became clear when we found that pre-cancerous cells lacking MNT had high levels of apoptotic cell death,” Dr. Hai Vu Nguyen said. “Thus, MNT is required to keep MYC-driven cells alive.” [2]
The researchers also examined the impact of depleting MNT from fully malignant MYC-driven lymphomas. They discovered that when MNT is removed that the tumor cells rapidly died. This was the light bulb moment: MNT could be the target.
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Citations
[1] Development and Survival of MYC-driven Lymphomas Requires MYC-Antagonist MNT to Curb MYC-induced Apoptosis. https://ashpublications.org/blood/article-abstract/doi/10.1182/blood.2019003014/440745/Development-and-Survival-of-MYC-driven-Lymphomas?redirectedFrom=fulltext
[2] Walter and Eliza Hall Institute. https://www.wehi.edu.au/news/new-front-opened-fight-against-common-cancer-driver