Preclinical studies on suicide gene therapy for head/neck cancer: A novel method for evaluation of treatment efficacy

Background: Malignancies of the oral cavity and oropharynx account for 31% of all diagnosed cancers in India. In most cases, patients present with tum ours that are clinically stage III/IV where surgery, radiotherapy and chemo therapy have not been very effective. Hence, there is an urgent need for al ternate treatment modalities. Gene therapy is a recent development shown to be effective in various malignancies. In this study we have attempted to c ause bulk reduction in tumour volume using the HSVtk/ganciclovir strategy, solely on the basis of the 'bystander' effect. Methods: Nude mouse xenograf t tumours of human head/neck cancer were engrafted with cells expressing vi ral thymidine kinase. After treatment with 8mM ganciclovir for 14 days, the treatment efficacy was monitored. A novel method has been devised to evalu ate cell kill microscopically in the whole tumour. Results: Of the 11 mice included in the study, 9 showed a significant reduction in fetal tumour vol ume of treated versus control tumours (p=0.015). Conclusions: Bulk reductio n in tumour load can be brought about without use of viral vectors for gene transfer solely by the bystander effect.