Researchers from the University of Cincinnati College of Medicine will be able to evaluate a new therapeutic approach in treating pancreatic cancer thanks to a recent grant from the Pancreatic Cancer Action Network (PanCAN).
The two-year, $300,000 grant will help Vladimir Bogdanov, PhD, associate professor and director of the Hemostasis Research Program within the Division of Hematology Oncology at the UC College of Medicine, continue his research focusing on targeting alternatively spliced Tissue Factor (asTF), a protein that promotes the formation of vascular networks that tumor cells often hijack to fuel their growth and spread.
"The overall objective of our proposal is to evaluate our recently developed monoclonal antibody targeting asTF, called RabMab1, as a new therapeutic approach in treating pancreas cancer,” says Bogdanov, who is also a member of the UC Cancer Institute and Cincinnati Cancer Consortium. "In addition, we hope to evaluate whether measuring asTF levels in the blood of pancreas cancer patients has predictive value and can serve as a tool for targeted therapies.”
He says that asTF expression and release into tissues is often increased in pancreatic cancer; asTF binds cell surface molecules, called beta1 integrins, in a specific region, triggering processes that drive cancer progression. Bogdanov adds that selectively blocking asTF reduced growth of pancreatic cancer in animal models.
"We will perform preclinical studies in animal models to determine the most effective way to deliver RabMab1, ensuring that it is beneficial; these preclinical studies are needed in order to launch clinical trials,” he says. "We will also evaluate the relationship between baseline asTF levels and progression-free survival in patients with stage IV pancreas cancer using patient tumor specimens.
"We will compare the expression of asTF at the very beginning of diagnosis and at time of progression. We think that elevation of asTF post-chemotherapy may be the mechanism of acquired resistance of pancreas cancer tumors that is activated under stress of exposure to agents that cause cell death. Our primary objective is to evaluate asTF protein levels in plasma and tumor biopsy samples as predictors of progression-free survival.”
Bogdanov says that if his theories are true, this research will set the foundation for Phase I and II clinical trials evaluating RabMab1 in patients with advanced pancreas cancer.
"This is exciting as we are one step closer to testing a new therapy in patients to benefit outcomes; it could also help us determine if asTF can be used as a biomarker in patients with all stages of pancreas cancer,” he says. "About 53,670 people will be diagnosed with pancreatic cancer in 2017, and about 43,090 people will die from it. We’re thankful for this funding which will hopefully help us come up with new and more effective treatments for this devastating disease.”
Sep 28, 2017