According to George Washington University researchers, the enzyme USP15 could potentially lead to new treatments for breast and pancreatic cancer.
USP15 is part of a group of deubiquitinylating enzymes, responsible for removing ubiquitin chains from proteins and other molecules, which play important roles in maintaining genome stability. Based on their research, Huadong Pei, Ph.D., senior author on the study published in Nature Communications today, and his team believe USP15 may function similarly to the USP4 enzyme, which was found to play a role in DNA repair by Pei's group four years ago.
"With this study, we validate the role of USP15 in maintaining genome stability and tumor suppression and inform novel treatments for breast cancer," said Pei, assistant professor of biochemistry and molecular medicine. "With consistent research and progress of current studies, we will gain a stronger understanding and a more comprehensive view of USP15 functions in cancer and their role in future treatment strategies."
The Cancer Genome Atlas indicates that USP15 enzyme deletions occur in 16% of breast cancers and in 5% of pancreatic cancers. Studies have shown that cancer-associated USP15 mutations increase poly ADP ribose polymerase (PARP) inhibitor sensitivity in cancer cells.
PARP inhibitors are a new class of pharmacological inhibitors developed for multiple purposes, but chiefly for the treatment of cancer. They have garnered a great deal of attention for their potential in the management of patients with BRCA mutations. Pei and his research team found that USP15 regulates homologous recombination—one of the major pathways to repair DNA damage affecting broth strands of the double helix—and cancer cell response to PARP inhibitors.
"USP15 is a potential biomarker for treatments of pancreatic cancer, as well as breast and ovarian cancers," explained Yihan Peng, a PhD student in Pei's lab and the first author on the study.