As we celebrate spring and the blooms to come, we are looking back at seeds planted through our Seed Grant Program, and are optimistic about the progress being made in pancreatic cancer research. Our 2019 Seed Grant cohort faced a difficult year for conducting research, establishing their labs and providing updates. We are catching up with these great scientists to share their progress and advances in pancreatic cancer research.
Steven R. Van Doren, PhD, a 2019 Seed Grant recipient at the University of Missouri has provided an update on his research including a published review on the importance of drug development that targets the protein-cutting enzyme MMP-7.
Recently published in Biochemical Society Transactions, Dr. Van Doren’s review explores the current research and understanding of the protease matrix metalloproteinase-7 (MMP-7). It is known that MMP-7 is secreted by tumor cells and that high levels in circulation correlate with poor prognosis and limited survival of patients with pancreatic ductal adenocarcinoma (PDAC). MMP-7 is required for the early acinar-to-ductal switch that leads to pancreatic tumorigenesis in mice, is present throughout tumor progression, and promotes tumor cell metastasis (spread of cancer to other areas of the body). In addition, high MMP-7 expression appears to be a marker of poor survival rates and may be predictive of unresectable tumors.
One area of research into treating pancreatic cancer is enhancing response to chemotherapies in order to increase surgical candidacy and prevent relapse post-surgical resection. MMP-7 protects cells from programmed cell death by targeting death signaling proteins from the surface of tumor cells. This appears to be one of the mechanisms by which pancreatic tumor cells are able to resist chemotherapy. Twenty years ago it was predicted that blocking MMP-7 could make pancreatic tumor cells more sensitive to chemotherapeutics. Recently, an anti-MMP-7 monoclonal antibody was shown to increase the susceptibility of several pancreatic cancer cell lines to chemotherapeutic drugs, by increasing their apoptosis (cell death) and decreasing migration.
Thanks to funding from the Hirshberg Foundation, Dr. Van Doren was also able to connect with Dr. Rolf Brekken at the University of Texas Southwestern Medical Center, a specialty center for investigations of pancreatic cancer using mouse models. Together, they have begun the early stages of drug screening and evaluation.
We are hopeful that this research brings progress to the treatment options available for pancreatic cancer. As Dr. Van Doren wrote, “I am grateful for the support from the Hirshberg Foundation to help enable this research. I am optimistic that targeting MMP-7 will advance treatment options” for all pancreatic cancer patients. It is thanks to your support that our momentum towards a cure continues.
