Researchers from the George Washington University (GW) Cancer Center found that deubiquitinase USP15 is a potential biomarker for the treatment of breast and pancreatic cancer.
USP15 is part of a group of deubiquitinases that are responsible for the removal of ubiquitin chains from proteins and other molecules that play an important role in maintaining genomic stability.
The Cancer Genome Atlas shows that USP15 is absent in 16% of breast cancers and 5% of pancreatic cancers. Studies have shown that the USP15 mutation associated with cancer promotes the sensitivity of poly ADP ribose polymerase (PARP) inhibitors in cancer cells.
PARP inhibitors are a class of versatile new drugs that are mainly used for cancer treatment, and their potential in treating patients with BRCA mutations has attracted great attention.
The team found that USP15 regulates homologous recombination, which is one of the main pathways for repairing DNA double-strand damage and, in addition, affects the response of cancer cells to PARP inhibitors.
"We validated the role of USP15 in maintaining genomic stability and tumor suppression and providing new treatments for breast cancer," the researchers said. “As the current research progresses, we have a deeper understanding and a more comprehensive understanding of the role of USP15 in cancer and its role in future treatment strategies.”
Next, the researchers will use a patient-derived tissue transplant model to study the effects of USP15 enzymes on radiochemotherapy. In addition, they will perform high-throughput screening of USP15 inhibitors.
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