Researchers at the University of California San Diego have discovered a potential new treatment target for triple-negative breast cancer (TNBC), a subtype known for its aggressiveness and lack of response to existing targeted therapies. The study, published in Cancer Research, identifies the protein PUF60 as essential for TNBC cell survival.
According to the research team, which includes Corina Antal, Ph.D., assistant professor, and Gene Yeo, Ph.D., professor at UC San Diego School of Medicine and members of UC San Diego Moores Cancer Center, PUF60 helps TNBC cells grow by controlling gene splicing. Disrupting this protein’s activity in laboratory models led to widespread errors in gene processing, DNA damage, cell-cycle arrest, and ultimately tumor cell death. Notably, healthy cells were largely unaffected when PUF60 was inhibited.
The researchers screened over 1,000 RNA-binding proteins in TNBC cells and identified 50 that are crucial for their survival. Among these, PUF60 stood out as a key candidate. Experiments involving either knocking down PUF60 or introducing mutations that disrupted its function resulted in significant DNA processing errors and tumor regression in multiple mouse models.
“By pinpointing PUF60 as a regulator that cancer cells depend on — but healthy cells do not — the findings suggest a new direction for future drug development,” the researchers said. “However, further research is needed to explore whether inhibitors targeting PUF60 or its splice-site interactions can be developed as targeted cancer therapies.”
TNBC remains one of the most challenging forms of breast cancer due to its aggressive nature and resistance to treatments like immunotherapy or hormone therapy used in other subtypes. The discovery highlights RNA splicing mechanisms as promising therapeutic angles not only for TNBC but potentially other cancers characterized by replication stress.
The study underlines the need for continued investigation into whether drugs targeting PUF60 could become viable treatment options.
