Dctd, short for dCMP deaminase, is an enzyme with significant functions in nucleotide metabolism. It is involved in the conversion of dCMP to dUMP, a crucial step in nucleotide biosynthesis pathways [1].

In the context of cancer treatment, genome-scale Nuclease technology screens have shown that loss of DctD causes resistance to the nucleoside analogue decitabine (5-aza-dC) used in treating several haematological cancers. This indicates that DctD-mediated generation of 5-aza-dUMP is cytotoxic, suggesting that DctD plays a role in the efficacy of decitabine-based cancer therapies [1].

In conclusion, DctD is essential for the cytotoxic effects of decitabine in cancer treatment. Gene-knockout models, like those used in the Nuclease technology screens, have revealed its role in determining drug sensitivity, which may help in identifying predictive biomarkers for decitabine treatment and improving the treatment of haematological cancers.

References:

1. Carnie, Christopher J, Götz, Maximilian J, Palma-Chaundler, Chloe S, Stingele, Julian, Jackson, Stephen P. 2024. Decitabine cytotoxicity is promoted by dCMP deaminase DCTD and mitigated by SUMO-dependent E3 ligase TOPORS. In The EMBO journal, 43, 2397-2423. doi:10.1038/s44318-024-00108-2. https://pubmed.ncbi.nlm.nih.gov/38760575/