A cure for pancreatic cancer is not possible, yet. For more than 80% of U.S. patients
diagnosed with unresectable pancreatic cancer, the average length of survival is less than one year. Even with well-established chemotherapeutic agent 5-Fluorouracil (5-FU) treatment, 95% of the patients will not be alive within five years. In recent clinical studies, interferon-α (IFN) therapy in conjunction with 5-FU has emerged as a
promising treatment strategy, but systemic toxicity and an unsustainable level of IFN in tumor sites remain serious challenges. Hence, we designed and cloned a novel adenovirus with replication restricted to Cox2-overexpressing pancreatic cancer cells as a vehicle system to deliver high dosage of IFN to only the pancreatic cancer cells, leaving the normal cells intact. We hypothesize that adenovirus expressing IFN in
combination with 5-FU would significantly enhance selectivity and anti-cancer effect of existing IFN-based regimens while reducing toxicity to healthy tissues. The cytocidal effect of the combination therapy on pancreatic cancer cells were analyzed in vitro by MTS assay. Eight days post-infection, the lone treatment of adenovirus
expressing IFN, the lone treatment of 5uM of 5-FU, and the combination therapy killed 21%, 10%, and 59% of pancreatic cancer cells, respectively. Remarkably, the adenovirus expressing IFN combined with 5-FU exhibited greater oncolysis than either of the treatments alone. Additional experimentation and assessment of the combination therapy may provide new insights into its efficacy. The combination
therapy possesses great potential in improving the long term survival of pancreatic cancer patients.
Funding for this project was provided by NIH/NIMHD through the P60 MD003422 “Center for Health Equity”, UAB/UMN SPORE in Pancreatic cancer CDA UCMED09060 (Davydova), NIH R01CA094084 (Yamamoto)
Han, Joohee; Armstrong, Leonard; Brown, Eric; Vickers, Selwyn; Yamamoto, Masato; Davydova, Julia.
A Novel Gene Therapy in Combination with Chemotherapeutic to Treat Pancreatic Cancer.
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