1997•International Journal of OncologyRequires access
Drug resistance to ganciclovir observed in suicide gene therapy is due to the loss of integrated herpes simplex virus-thymidine kinase gene
M Kimura, Masatoshi Tagawa, Keizo Takenaga, Akira Nakagawara, Keisuke Horitsu, T Yamaguchi, Hiromitsu Saisho, Shigeru Sakiyama
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Abstract
Human pancreatic cancer cells (AsPC-1) expressing the herpes simplex virus-thymidine kinase (HSV-TK) gene were inoculated into nude mice and ganciclovir (GCV) was administrated for the treatment. At the initial course of treatment we observed a notable reduction of tumor masses. However, therapeutic effect of GCV to the recurrent tumors decreased significantly. This reduced sensitivity of the AsPC-1/HSV-TK cells to GCV was also confirmed by an in vitro test. Examination of HSV-TK gene in the drug resistant cells showed a loss of the integrated gene. These data indicate that repeated GCV administration results in the loss of integrated HSV-TK gene and confers GCV resistance.