The role of herpes simplex virus thymidine kinase in the treatment of solid tumours.
Suicide gene therapy is the approach whereby the genetic alteration of a cell renders it susceptible to an otherwise non-toxic prodrug. Suicide gene therapy for solid tumours has progressed rapidly since the concept was originally described: nearly all tumour types have been explored, with some, such as glioma, melanoma and colon cancer frequently used experimentally. The exciting aspect of suicide gene therapy is the bystander effect, the phenomenon whereby there is extended tumour death when only a small fraction is transfected with the suicide gene. This phenomenon implies that there is a reduced need to target specifically all tumour cells, as the effect mechanism itself carries out this function. The bystander effect mode of action has not yet been fully characterised, but the role of gap junctions and the immune system are implicated as the main instruments in its potentiation. This approach is also amenable to pharmacological intervention, which may help to optimise parameters prior to commencing suicide gene therapy. Clinical trails have already commenced using this form of treatment and results are eagerly awaited.
Department of Urology, St George's Hospital Medical School, Cranmer Terrace, London SW17 0QT, UK. mperry@sghms.ac.uk
M J
MJ
Perry
S M
SM
Todryk
A G
AG
Dalgleish