Deoxycytidine kinase (dCK) is an enzyme in the nucleoside biosynthetic pathway. It catalyzes the phosphorylation of cytarabine to cytarabine monophosphate, a crucial step for the eventual incorporation of cytarabine triphosphate into DNA, and is involved in the salvage pathway for nucleotide production [2]. It also has a role in the activation of gemcitabine by phosphorylation and is associated with the regulation of the NRF2/ARE axis and ROS production [5,4].

In cancer research, dCK has emerged as a significant factor. In BRCA2-deficient cancers, inhibition of dCK is synthetic lethal, suggesting it could be a new target for these cancers, different from the mechanism of PARP inhibitors [1]. In acute myeloid leukemia, DCK mutations can lead to cytarabine resistance, and overexpression of wild-type DCK can restore cytarabine sensitivity [2]. In gemcitabine-resistant cancer cells, DCK is frequently inactivated, and its inactivation is one of the crucial mechanisms in acquiring gemcitabine resistance [5]. In pancreatic ductal adenocarcinoma, dCK protein expression is positively correlated with overall survival and disease-free survival, and the A9846G AA genotype in the dCK gene is associated with reduced mortality [6]. Also, in meningiomas, high expression of dCK is related to high gemcitabine sensitivity, stronger tumor cell proliferative activity, and shorter survival in patients [3].

In conclusion, dCK is essential in nucleotide-related processes and has a profound impact on cancer-related mechanisms, including drug resistance and prognosis. Studies, especially those on gene mutations and expression changes in various cancer models, have revealed its significance in understanding and potentially treating different cancers.