TK1 in gastric cancer: Helicobacter pylori-driven oncogenesis biomarker, utility, and emerging targeted therapies

As a leading cause of cancer-related mortality among gastrointestinal malignancies, gastric carcinoma (GC) necessitates enhanced molecular diagnostic paradigms for early intervention. The thymidine kinase enzymatic family, particularly thymidine kinase 1 (TK1, EC 2.7.1.21), serves as an enzymatic orchestrator of deoxyribonucleotide salvage pathways critical for genomic integrity maintenance, and its oncogenic overexpression acts in concert with <i>Helicobacter pylori</i>-mediated chronic inflammatory microenvironments, and potentiates the histopathological progression from premalignant metaplasia review delineates the utility of TK1 as a serological biomarker for early detection, tumor staging, therapeutic monitoring, and prognostic stratification in GC. We have hypothesized the molecular mechanisms underlying TK1-mediated oncogenesis and its interplay with <i>H. pylori</i>-induced pathogenesis. Additionally, we have explored emerging TK1-targeted therapeutic modalities, including gene-directed enzyme prodrug therapy (GDEPT), nanoscale drug delivery platforms, and adoptive cell therapy, while evaluating TK1's translational potential in GC management. Although the precise regulatory networks of TK1 in gastric carcinogenesis remain incompletely characterized, ongoing research positions TK1 as a promising diagnostic and therapeutic target, potentially revolutionizing strategies to ameliorate clinical outcomes.