Pancreatic cancer is an especially lethal disease with a five-year survival rate of less than 9.2% and a median survival of only 5-6 months. The poor prognosis is due to early and aggressive invasion, accompanied by late clinical presentation and resistance to chemotherapies and radiotherapies. Current surgery and chemotherapy/radiotherapy-based clinical strategies are not efficient and suffer from dose-limiting toxicities, desmoplasia, and drug resistance. Therefore, there is an urgent need to develop alternative therapies to treat lethal pancreatic cancer and improve clinical outcomes.
Repurposing existing drugs is an efficient, time-saving, and economical strategy. Anthelminthic antiparasitic drugs have been shown to act as anticancer drugs, presenting a promising option for cancer treatment. Niclosamide, a medication to treat tapeworm infestations, has demonstrated anticancer potential by inhibiting multiple signaling pathways. Our preliminary data along with other studies in the literature on pancreatic cancer and other cancer cell lines have shown that niclosamide significantly inhibited several signaling pathways such as Stat3, Wnt/β-catenin, sonic hedgehog, c-Jun-ROS, NFκB, AKT/mTOR/ERK, Stat3, notch, mitochondrial respiration, glucose utilization, cellular stress, and cancer stem cells, which play an important role in pancreatic cancer pathogenesis, desmoplasia, and metastases. But despite its anticancer potential, niclosamide has poor bioavailability and high doses cause severe side reactions such as nausea, diarrhea, and colitis.
In collaboration with Dr. Surya Mallapragada at Iowa State, we developed a nanotechnology-based approach using polyanhydride nanoparticles loaded with niclosamide to enhance bioavailability and specific targeting to cancer cells. The chemistry of biocompatible nanoformulations can be tailored and functionalized to control the surface erosion and niclosamide release rate as well as to enable targeted drug delivery and improved bioavailability. This research is expected to pave the way for alternative and efficient pancreatic cancer treatments.
“Pancreatic cancer: targeting the tumor and its microenvironment using nanotherapeutics”
Satyanarayana Rachagani, PhD
Assistant Professor of Biochemistry and Molecular Biology, University of Nebraska Medical Center
Thursday, August 26th, 3:00 – 4:00 PM CT