"RHAMM knockout" mice express a truncated RHAMM protein that promotes pancreatic cancer progression with dysfunctional p53.

Pancreatic cancer, which lacks effective treatment, has the highest mortality rate of all major cancers (1). A recent study by Lin et al. published in Cancer Letters (2) sought out to investigate whether RHAMM is a therapeutic target in pancreatic cancer using a Rhamm −/− mouse strain. Surprisingly, a truncated HMMR Δexon8–16 protein expressed at higher levels than wild-type RHAMM protein was found in this “knockout” strain and HMMR Δexon8–16 accelerated pancreatic cancer progression in genetic engineered mouse models. Pancreatic cancer is projected to become the second leading cause of cancer-related death by 2030 (3). The most common type of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC). Pancreatic neuroendocrine tumor (PNET) is the second common malignancy of pancreas and its incidence is increasing (4). Pancreatic cancer patients are often diagnosed at advanced stages. Despite intense efforts in improved diagnostic methods and development of targeted therapies, the overall survival for pancreatic cancer has changed little. It is critical to understand the biology of pancreatic cancer and identify novel therapeutic targets for this devastating disease.