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Citydine deaminase expression level in cancer as a new biomarker predicting efficacy of anti-cancer agents

Institut Curie
07/03/2017
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The present invention relates to the field of medicine, in particular of oncology. It concerns improvements in the treatment of cancer with high and low CDA (Cytidine Deaminase) expression level and the selection of patients for such treatments, kits and methods for screening compounds useful to improve treatment of cancer with high or low CDA expression level
 Plateforme de criblage phénotypique Biophenics
Plateforme de criblage phénotypique Biophenics dirigée par Elaine Del Nery dans le département de Recherche translationnelle. Cette plateforme repose sur l'expertise de l'Institut Curie en biologie cellulaire. Grâce à l'automatisation de la prise d'images couplées à des algorithmes d'analyse d'images, la biologie cellulaire est mise au service de la validation de cibles et de l'identification de molécules chimiques actives plus sélectives.

Opportunity

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

Background

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).

Competitive advantages

CDA status by IHC

Intellectual Property

Patent filed in March 2016

References

Cytidine deaminase deficiency reveals new therapeutic opportunities against cancer. Clinical Cancer research, Sep 6 2016,

R&D Status

R&D status Poc In vivo