To date, no biomarker has been identified that is specific enough to detect pancreatic cancer at an early stage and no reliable treatments. In hopes of changing survival rates, the Ohio State Wexner Medical Center researcher Zobeida Cruz-Monserrate, PhD, has been awarded multiple grants to understand why pancreatic cancer cells express specific proteins, explore whether those proteins could serve as early detection biomarkers and discover if blocking them could serve as effective therapy.
A five-year, $1.78 million R01 grant from the National Cancer Institute funds the first study from Dr. Cruz-Monserrate, director of the Molecular and Cellular Biology Program and Laboratory in the Division of Gastroenterology, Hepatology and Nutrition (GHN) at The Ohio State University, as well as a member of the Molecular Carcinogenesis and Chemoprevention Program at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).
The study explores the role of a protein called lipocalin 2 (LCN2) in pancreatic ductal adenocarcinoma (PDAC), which grows in a complex tumor microenvironment (TME) that’s poorly understood at the molecular level. As a result, effective prevention and treatment therapies remain elusive.
According to materials provided by the Cruz-Monserrate Lab:
- Pancreatic stellate cells (PSC) are key mediators of inflammation and the fibrotic stroma in the TME.
- The lab’s long-term goal is to understand molecular "cross talk" among cells in the PDAC TME—with particular focus on LCN2.
- This understanding may then guide development of effective therapies that block LCN2 and/or LCN2-associated pathways.
“If we can confirm that LCN2 can serve as a reliable target for the treatment of pancreatic cancer, we could then develop new interventions that are in such a dire need for this disease,” Dr. Cruz-Monserrate says.
The second study, a two-year R21 grant awarded by the National Cancer Institute, will allow the Cruz-Monserrate Lab to explore the development of cachexia in pancreatic patients. Characterized by the dramatic loss of skeletal muscle mass and extreme weight loss, cachexia can account for up to a third of all cancer deaths and is particularly prevalent in pancreatic cancer patients.
“Early in my career, I met and interacted with surgeons who explained how devastating pancreas cancer was and how my research could one day help make a difference,” Dr. Cruz-Monserrate says. “That’s when my passion toward this disease started and continues to this day. As with the other studies in our lab, my hope is that our findings relative to cachexia can one day directly translate into effective therapies in a clinical setting.”
A third new funding mechanism for the Cruz-Monserrate Lab is an intramural research program (IRP) awarded by the OSUCCC – James and funded by Pelotonia. IRP awards are intended to foster innovation and discovery by providing the seed money needed to develop promising research and to generate preliminary data and publications that will make them competitive for NCI grants.
“Adipose tissue can also secrete the pro-inflammatory factor LCN2, which could be influencing tumor development in obese individuals,” Dr. Cruz-Monserrate explains. “This research project will focus on which secreted factors from the adipose tissue elicit cancer growth so we can better understand the role of obesity in the initiation, progression and prevention of pancreatic cancer, since obesity is known to increase the risk of pancreatic cancer development.”
A fourth study, in collaboration with H. Lee Moffitt Cancer Center & Research Institute and funded by the Oncology Research Information Exchange Network® (ORIEN) New Oncologic Visionary Awards (NOVA) program, explores the protease activity and genomic expression of molecules in tumors for the early detection of pancreatic cancer in high-risk pancreatic cystic lesions.
“I have been extremely fortunate to have my academic appointment as assistant professor be within the Department of Internal Medicine Division of Gastroenterology Hepatology and Nutrition,” Dr. Cruz-Monserrate says. “My close collaboration with clinicians has facilitated discussions about the most critical clinical needs of pancreatic cancer patients. These partnerships were crucial to the development of all these studies and will continue to fuel successful execution of each moving forward.”