Transduction of the herpes thymidine kinase gene into premalignant murine mammary epithelial cells renders subsequent breast cancers responsive to ganciclovir therapy.
Drug sensitivity ("suicide") genes can sensitize cancer cells to chemotherapy, but therapeutic use of these genes is limited by difficulties in delivering them to all areas of established cancers. An alternative strategy entails preemptive introduction of suicide genes into tissues at risk for cancer, thereby imparting drug sensitivity as a clonal property to cancers arising from sensitized cells. To test the preemptive approach, a retroviral vector was used to transduce the herpes thymidine kinase gene into the TM4 line of preneoplastic murine mammary epithelial cells to yield a clonal subline sensitized to the guanosine analog ganciclovir. Ganciclovir therapy of tumors that arose from the transduced cells retarded tumor growth and induced durable regressions in 7/20 mice; ganciclovir was ineffective against control tumors. The results imply the possibility of reducing cancer lethality by actions taken before cancers arise.
Moolten
F L
FL
Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA 01730, USA.
Vonderhaar
B K
BK
Mroz
P J
PJ
D000818:Animals; D000963:Antimetabolites / Q000627:therapeutic use* / Q000633:toxicity; D002460:Cell Line; D004847:Epithelial Cells; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use* / Q000633:toxicity; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006564:Herpesviridae / Q000201:enzymology; D008321:Mammary Glands, Animal / Q000166:cytology; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D011230:Precancerous Conditions; D011355:Prodrugs / Q000627:therapeutic use; D012190:Retroviridae / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism
D000963:Antimetabolites; D011355:Prodrugs; D013937:Thymidine Kinase; D015774:Ganciclovir