Viral vectors in pancreatic cancer gene therapy

摘要

Pancreatic cancer is the fourth leading cause of cancer related deaths, and effective diagnostic and therapeutic strategies are lacking. Molecular research seeking genetic events and signaling pathways that are crucial in pancreatic carcinogenesis holds promise for the development of effective gene therapy strategies. The success of such strategies will depend on efficient, specific, and safe gene delivery to target cells as well as improved target cell- specific gene expression. Adenoviral vectors and retro/lenti-viral vectors have gained significant popularity in cancer gene therapy strategies because of their superior gene transfer efficiency and stable gene expression property, respectively. Many studies have been done to deliver tumor suppressor genes or suicide genes using adenovirus or retro/lenti-virus vectors to treat pancreatic cancer. Another promising therapeutic strategy for pancreatic cancer is the use of conditionally replicating (oncolytic) viruses. These viruses can selectively replicate in cancer cells, and their progeny viruses subsequently spread to surrounding cells, therefore achieving a large scale of viral infection. Several viruses, including adenovirus, herpes simplex virus (HSV), and reovirus have been modified for oncolytic purpose, and incorporation of extra tumoricidal strategies such as enzyme-directed pro-drug and fusogenic viral glycoproteins can further potentiate their anti-tumor capacity. This review provides a brief overview of gene therapy strategies using different viral vectors and anti-tumor activities of oncolytic viruses for pancreatic cancer treatment.