Researchers at the University of California San Diego have found a new potential treatment target for triple-negative breast cancer (TNBC), a form of breast cancer known for its aggressiveness and lack of effective targeted therapies. The study identifies the protein PUF60 as essential for TNBC cell survival, with its disruption leading to DNA damage and death in tumor cells while leaving healthy cells largely unaffected.
TNBC is considered one of the most challenging types of breast cancer to treat because it does not respond to therapies like immunotherapy or hormone therapy that are available for other subtypes. This often results in poor outcomes for patients, prompting researchers to search for new approaches that focus on the molecular mechanisms supporting cancer cell survival.
The research team screened over 1,000 RNA-binding proteins in TNBC cells and found 50 critical to the cancer’s survival, highlighting PUF60 as a key candidate. When they reduced PUF60 activity or introduced specific mutations, they observed major errors in gene processing and cell death in laboratory models. In mouse models, loss of PUF60 led to significant regression of tumors, while healthy breast cells were mostly unaffected.
The findings point to PUF60-mediated RNA splicing as a promising area for developing future treatments targeting TNBC and possibly other cancers marked by replication stress. Researchers caution that more studies are needed to determine if drugs can be designed to inhibit PUF60 or its interactions effectively.
The study was published in Cancer Research and led by Corina Antal, Ph.D., assistant professor, and Gene Yeo, Ph.D., professor at UC San Diego School of Medicine. Both are also members of UC San Diego Moores Cancer Center.
