Citydine deaminase expression level in cancer as a new biomarker predicting efficacy of anti-cancer agents
The inventors focused on CDA underexpression and CDA overexpression and identified new subgroups of cancers. Cancer expressing:
- Low level of CDA were susceptible to the specific toxic effects of a group of drugs such as aminoflavone (repurposing project)
- High level of CDA were susceptible to the specific toxic effects of another group of drugs including molecules already approved on the market
Cytidine deaminase (CDA) is an enzyme of the pyrimidine salvage pathway catalyzing the hydrolytic deamination of cytidine and deoxycytidine to uridine and deoxyuridine, respectively (Demontis S et al, Biochim Biophys Acta, 1998, 1443:323–33). CDA plays an important role in the sensitivity/resistance of cancer cells to treatment with cytidine analogs, and CDA overexpression has been reported to be a good marker for resistance to chemotherapy based on cytidine analogs (Neff T and Blau CA, Exp Hematol. 1996; 24:1340–6; Weizman N et al., Oncogene. 2014; 33:3812–9).
CDA status by IHC
Patent filed in March 2016
Cytidine deaminase deficiency reveals new therapeutic opportunities against cancer. Clinical Cancer research, Sep 6 2016,