Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes: paradigm for a prospective cancer control strategy.

The lack of highly exploitable biochemical differences between normal tissues and some tumors can theoretically be circumvented by a strategy utilizing gene insertion prophylactically to create tissue mosaicism for drug sensitivity, thereby ensuring that any tumor arising clonally will differ from part of the normal cell population. Elements of the strategy were tested with neoplastic BALB/c murine cell lines bearing the herpes thymidine kinase gene. Exposure to the herpes thymidine kinase-specific substrate 9-([2-hydroxy-1-(hydroxymethyl)ethoxy]methyl)guanine ablated the clonogenic potential of the cells in vitro, and administration of this drug to BALB/c mice bearing tumors produced by the cell lines uniformly induced complete regression of the tumors. The observed responses to therapy imply that the strategy may prove valuable when the genetic technology needed for its human implementation becomes available.