Researchers from The Jackson Laboratory (JAX) and UConn Health have uncovered how cancer disrupts RNA splicing—a process crucial for protein production—to drive tumor growth. Their findings introduce a promising new therapy that could halt or even shrink aggressive tumors, offering hope for patients with limited treatment options.

RNA splicing allows cells to create diverse proteins from a single gene by selecting which sequences to retain. In healthy cells, this process is tightly controlled, ensuring proper protein regulation. However, cancer manipulates this mechanism, silencing key genetic "off switches" known as poison exons. These exons normally prevent harmful protein buildup, but their suppression enables tumors to thrive.

The research, led by Dr. Olga Anczukow and her team, identified that cancer cells deactivate poison exon activity in the TRA2b gene, leading to unchecked tumor proliferation. They also found that lower poison exon levels correlate with poorer patient outcomes in aggressive cancers, including breast, brain, ovarian, and skin cancers.

To counteract this, the scientists developed a strategy using antisense oligonucleotides (ASOs)—synthetic RNA fragments that restore poison exon function. When introduced into cancer cells, ASOs reactivated the genetic "kill switch," effectively reducing tumor growth. Unlike direct protein removal, which failed to halt tumors, targeting RNA proved more effective, suggesting a new approach for treatment.

Further research is needed to refine ASO-based therapies and optimize their delivery to tumors. However, initial findings indicate that ASOs are highly specific and do not disrupt normal cellular functions, making them a promising avenue for future cancer treatments.