Herpes simplex virus type 1 thymidine kinase (HSV-TK) (HSV-TK)

Herpes simplex virus type 1 thymidine kinase (HSV-TK) is a viral enzyme that serves as the primary component of a widely studied suicide gene therapy system for cancer (Fillat et al., 2003). In this therapeutic approach, the HSV-TK gene is delivered to tumor cells via a vector, such as an adenovirus (ADV-TK), leading to the expression of the viral enzyme within the malignant tissue (Aguilar et al., 2015). Unlike human thymidine kinase, HSV-TK has a broad substrate specificity and can efficiently phosphorylate nucleoside analogs like ganciclovir into monophosphate forms (UniProt P03176). These monophosphates are then converted by endogenous cellular kinases into cytotoxic triphosphate metabolites that act as DNA chain terminators, specifically killing cells during the S-phase of the cell cycle (Wyzewski et al., 2021). A significant advantage of this system is the "bystander effect," where the toxic metabolites are transferred to neighboring non-transduced tumor cells through gap junctions, thereby enhancing the overall anti-tumor efficacy (Moolten, 1986). This target is primarily utilized in the treatment of solid tumors, including glioblastoma and prostate cancer, and its activity can be monitored non-invasively using specialized PET imaging tracers like [18F]FHBG (Yaghoubi et al., 2006).

Other names

HSV1-TKThymidine kinase 1 (viral)Suicide geneType 1 thymidine kinaseADV-TKGanciclovir kinase

The enzyme acts as a suicide gene by phosphorylating nucleoside analog prodrugs (e.g., ganciclovir) into monophosphates, which are then converted by host kinases into cytotoxic triphosphates that terminate DNA chain elongation and induce apoptosis.