Cancer is the second leading cause of death in the U.S., claiming around 600,000 lives in 2022 alone. A diagnosis can be devastating, as the disease can often resist treatment and spreads uncontrollably.
Now, a research team from The Jackson Laboratory (JAX) and UConn Health has identified a potential therapeutic strategy to halt or reverse tumor growth. Their study, published in Nature Communications, reveals how cancer cells disable a built-in "off switch" — and how reactivating it could stop tumor proliferation.
Overriding the "Off Switch"
Cells function through an intricate network of proteins, each designed for specific tasks like metabolism, tissue repair, and immune defense. These proteins are built using genetic blueprints in our DNA. A process called alternative splicing enables a single gene to generate multiple mRNA transcripts — molecules carrying genetic instructions — allowing for protein diversity.
In healthy cells, this process maintains balance. Cancer cells, however, disrupt that process to fuel their unchecked growth by disabling proteins that regulate cell proliferation.
The researchers focused on a genetic element known as a poison exon. This natural "off switch" prevents the production of certain proteins by marking their RNA messages for destruction before they can be translated. Cancer cells suppress the poison exon in a key gene called TRA2β. Without this regulation, TRA2β levels rise, promoting tumor growth and making cancer cells more aggressive.
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A New Target for Precision Treatment
TRA2β is a well-known oncogene — a gene that can drive cancer development — but no existing therapies specifically target it. Until now, scientists had limited understanding of how it is regulated.
By analyzing data from The Cancer Genome Atlas, researchers discovered that the status of the poison exon in TRA2β could serve as a meaningful target for precision oncology.
“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,” said Olga Anczuków, an associate professor at JAX in a press release.
To test whether reactivating the "off switch" could slow cancer growth, the team designed synthetic RNA fragments called antisense oligonucleotides (ASOs). These molecules were engineered to boost poison exon activity in TRA2β, restoring the gene's self-regulating mechanism.
The team tested this approach in 3D breast cancer organoids — clusters of cancer cells that mimic real tissue — and in live mouse models.
The results were promising: “We found that ASOs can rapidly boost poison exon inclusion, essentially tricking the cancer cell into turning off its own growth signals. That could make ASOs a highly precise and effective therapy for aggressive cancers,” said Nathan Leclair, an M.D./Ph.D. graduate student at UConn Health and The Jackson Laboratory, and lead author of the study, in a news release.
The Future of "Off Switch" Therapies
If TRA2β drives tumor growth, why not eliminate it entirely using gene-editing technologies like CRISPR? The researchers attempted this approach but found that the tumors continued to grow.
“This tells us that poison-exon-containing RNA doesn’t just silence TRA2β,” explained Anczuków in the press release. “It likely sequesters other RNA-binding proteins, creating an even more toxic environment for cancer cells.”
Ongoing research aims to optimize ASO-based therapies and explore the most effective ways to deliver them to tumors. Early findings suggest that ASOs selectively target cancer cells while sparing healthy ones, positioning them as a promising tool for future cancer treatments. This discovery could revolutionize treatment for aggressive cancers like triple-negative breast cancer and certain brain tumors, where current options remain limited.
By leveraging the body's own genetic safeguards, scientists may have found a powerful new way to combat some of the most challenging cancers. While further studies are needed, this breakthrough offers a glimpse into the future of precision oncology.
Read More: CRISPR Eliminates Targeted Tumors by 50 Percent
Article Sources
Our writers at Discovermagazine.com use peer-reviewed studies and high-quality sources for our articles, and our editors review for scientific accuracy and editorial standards. Review the sources used below for this article:
The Jackson Laboratory: What is CRISPR?
National Center for Health Statistics: Cancer
National Human Genome Research Institute: The Cancer Genome Atlas
Nature Communications: Antisense oligonucleotide-mediated TRA2β poison exon inclusion induces the expression of a lncRNA with anti-tumor effects
Having worked as a biomedical research assistant in labs across three countries, Jenny excels at translating complex scientific concepts – ranging from medical breakthroughs and pharmacological discoveries to the latest in nutrition – into engaging, accessible content. Her interests extend to topics such as human evolution, psychology, and quirky animal stories. When she’s not immersed in a popular science book, you’ll find her catching waves or cruising around Vancouver Island on her longboard.
