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Scientists have made a significant breakthrough in cancer research, discovering a method to reactivate a molecular “kill switch” within cancer cells, potentially offering a new therapeutic strategy for aggressive tumors. The research, published in the February 15th issue of Nature Communications, details how manipulating RNA splicing can trigger the destruction of cancer-promoting proteins.
The study, conducted by scientists from The Jackson Laboratory (JAX) and UConn Health, focuses on alternative RNA splicing, a process where cells create diverse proteins from a single gene. In cancer, this process malfunctions, fueling tumor growth. The team found that cancer cells suppress “poison exons,” genetic elements that naturally inhibit protein production. By restoring the activity of these poison exons, particularly in the TRA2β gene, researchers were able to disrupt cancer cell proliferation.
“We’ve shown for the first time that low levels of poison exon inclusion in the TRA2β gene are associated with poor outcomes in many different cancer types, and especially in aggressive and difficult-to-treat cancers,” explained Olga Anczuków, an associate professor at JAX and co-program leader at the NCI-designated JAX Cancer Center. These cancers include triple-negative breast cancer, brain tumors, ovarian cancers, skin cancers, leukemias, and colorectal cancers.
The researchers used antisense oligonucleotides (ASOs), synthetic RNA fragments, to increase the inclusion of poison exons in the TRA2β gene. This effectively “tricked” cancer cells into turning off their own growth signals.
“We found that ASOs can rapidly boost poison exon inclusion, essentially tricking the cancer cell into turning off its own growth signals,” said Nathan Leclair, an MD/Ph.D. graduate student at UConn Health and The Jackson Laboratory who spearheaded the research. “These poison exons work like a rheostat, quickly adjusting protein levels—and that could make ASOs a highly precise and effective therapy for aggressive cancers.”
Interestingly, experiments using CRISPR gene editing to completely remove TRA2β proteins resulted in continued tumor growth, suggesting that targeting the RNA through poison exon activation is a more effective strategy. This indicates that the poison exon-containing RNA likely plays a broader role in suppressing tumor growth beyond simply silencing TRA2β.
Further studies are planned to refine ASO-based therapies and determine optimal delivery methods. Preliminary data suggest that ASOs are highly specific and do not interfere with normal cellular function, making them promising candidates for future cancer treatments.
More information: Nathan K. Leclair et al, Antisense oligonucleotide-mediated TRA2β poison exon inclusion induces the expression of a lncRNA with anti-tumor effects, Nature Communications (2025). DOI: 10.1038/s41467-025-56913-8
Journal information: Nature Communications
Disclaimer: This article is based on preliminary research findings. While the results are promising, it is important to note that further research and clinical trials are necessary before this approach can be considered a viable cancer treatment. The information provided should not be interpreted as medical advice. Always consult with a healthcare professional for any health concerns.
