Pancreatic cancer is notoriously aggressive and difficult to treat, underscoring the need for more effective therapeutic targets. Research led by Jie Fu, Ph.D., Jianhua Ling, Ph.D., and Paul Chiao, Ph.D., previously showed that apoptosis, or cell death, resistance in KRAS G12D-mutant pancreatic cancer was accelerated by deleting the Plk3 tumor suppressor, but the regulatory mechanism of Plk3 activation remains unknown.
To provide further insights, the researchers examined the role of Plk3 in KRAS G12D-mutant pancreatic cancer models. They found that the nardilysin (NRDC) enzyme cuts a Plk3 precursor, resulting in Plk3 activation that promotes apoptosis and suppresses cancer progression and metastasis. The study provides insights into this post-translational modification, highlighting NRDC and Plk3 as potential biomarkers for prognosis and treatment response. The findings suggest that targeting this pathway is a potential therapeutic strategy for patients with KRAS G12D-mutant pancreatic cancer.