Combination treatment of human pancreatic cancer xenograft models with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib and oncolytic herpes simplex virus hf10

摘要

Background: There is the potential to use replication-competent oncolytic viruses to treat cancer. We evaluated the efficacy of HF10, a herpes simplex virus type 1 (HSV-1) mutant, in combination with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in human pancreatic cancer xenograft models. Methods: The viability of human pancreatic cancer cell lines (BxPC-3 and PANC-1) treated with HF10 and erlotinib, on their own or in combination, was determined. Effects of erlotinib on HF10 entry into tumor cells were also investigated. BxPC-3 subcutaneous tumor-bearing mice were treated with HF10 and erlotinib, on their own or in combination, with effects on tumor volume determined. Immunohistochemical examination of HSV-1 and CD31 was conducted to assess virus distribution and angiogenesis within tumors. A peritoneally disseminated BxPC-3 xenograft model was evaluated for survival. Results: HF10 combined with erlotinib demonstrated the highest cytotoxicity against BxPC-3. A combination effect was not observed in PANC-1 cells, and erlotinib did not affect virus entry into tumor cells. In the peritoneally disseminated model, HF10 combined with erlotinib had no beneficial effect on survival. In the subcutaneous tumor model, combination therapy resulted in the inhibition of tumor growth to a greater extent than using each agent on its own. Immunohistochemistry revealed that virus distribution within the tumor persisted in the combination therapy group. Conclusions: Combination therapy with HF10 and erlotinib warrants further investigation to establish a new treatment strategy against human pancreatic cancers.