UC San Diego scientists have uncovered a previously overlooked target for the most aggressive form of breast cancer, offering hope for future drug development.
The breakthrough, led by UCSD School of Medicine assistant professor Corina Antal and professor Gene Yeo, marks the first study the married couple have co-led. Their findings, recently published in Cancer Research, focus on a protein called poly(U)-binding splicing factor 60 (PUF60), which could hold the key to combating triple-negative breast cancer (TNBC).
“PUF60 acts like an editor, making sure important sequences in the cell’s instruction manual are not accidentally removed,” Antal explained. “It’s involved in correctly splicing transcripts essential for DNA repair and cell cycle regulation. When splicing goes awry, cells accumulate DNA damage and die.”
TNBC is notoriously aggressive and does not respond to standard targeted therapies such as immunotherapy or hormone treatments, according to UC San Diego Health. For Antal, the research carries personal significance—her mother passed away from TNBC more than a decade ago.
To identify potential targets, the research team screened roughly 1,000 RNA-binding proteins in TNBC cells using integrative CRISPR technology and RNA sequencing. Of these, 50 proteins were essential for cancer survival, with PUF60 emerging as the top candidate.
“We systematically turned off hundreds of RNA-binding proteins in cells and tumors in mice to see which proteins were critical for cancer cells but not for normal cells,” Antal said. “PUF60 stood out because it is expressed at higher levels in cancer cells, and patients with elevated PUF60 tend to have poorer survival outcomes.”
Experimental disruption of PUF60—either through targeted knockdown or specific mutations—led to severe DNA processing errors and ultimately cell death in TNBC models, highlighting its potential as a therapeutic target.
Yeo outlined the team’s next steps: investigating PUF60’s role in other cancer types, testing drug interactions targeting the protein, and exploring new chemical compounds that could affect its activity. He emphasized that advancing these findings into clinical therapies will require robust funding.
“With federal funding and venture investment fluctuating, increased philanthropic support is critical,” Yeo said. “There’s a significant gap between academic discoveries and clinical application. Without sustained support, promising research can stall halfway.”
This discovery opens a promising new avenue for TNBC treatment, potentially offering a lifeline for patients facing one of the most challenging forms of breast cancer.
