Researchers at the University of California San Diego have identified a new potential treatment target for triple-negative breast cancer (TNBC), which is known as the most aggressive form of breast cancer. According to a recent study, the protein PUF60 is essential for TNBC cells to grow and survive because it controls how key genes are spliced. The researchers found that when they disrupted PUF60 activity in models of TNBC, it led to widespread errors in gene processing, DNA damage, cell-cycle arrest, and eventually tumor cell death. Healthy cells were not affected by this disruption.
TNBC is considered difficult to treat because it does not respond to targeted therapies like immunotherapy or hormone therapy that are effective against other types of breast cancer. As a result, patients with TNBC often have limited treatment options and poor outcomes. Researchers are therefore seeking new ways to target the disease by focusing on the molecular mechanisms that help cancer cells survive.
The study highlights PUF60-mediated RNA splicing as a promising area for developing future treatments for TNBC and possibly other cancers characterized by replication stress. By identifying PUF60 as a regulator that is crucial for cancer cells but not healthy ones, the findings suggest new possibilities for drug development. However, further research will be necessary to determine whether inhibitors targeting PUF60 or its splice-site interactions can be developed into effective targeted therapies.
The research was published in Cancer Research and led by Corina Antal, PhD, assistant professor, and Gene Yeo, PhD, professor at UC San Diego School of Medicine. Both are also members of UC San Diego Moores Cancer Center.
